Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all

Gil, Jesús; Peters, Gordon

doi:10.1038/nrm1987

Cited by 845Cancer-related Molecular PathwaysTelomeres, Telomerase, and SenescenceChromatin Remodeling and Cancer

Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all

Gil, Jesús, Peters, Gordon·2006·Nature Reviews Molecular Cell Biology

DOI 10.1038/nrm1987

Open this paper in CoChat — free account

Abstract

The INK4b-ARF-INK4a locus encodes two members of the INK4 family of cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a), and a completely unrelated protein, known as ARF. All three products participate in major tumour suppressor networks that are disabled in human cancer and influence key physiological processes such as replicative senescence, apoptosis and stem-cell self-renewal. Transcription from the locus is therefore kept under strict control. Mounting evidence suggests that although the individual genes can respond independently to positive and negative signals in different contexts, the entire locus might be coordinately suppressed by a cis-acting regulatory domain or by the action of Polycomb group repressor complexes.

Integrity signals

Registry

Crossref · 10.1038/nrm1987

Cites

150 of 150 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Most cancers harbor mutations in one or both of the p53 or p16INK4a/pRB pathways.
“Most cancers harbor mutations in one or both of these pathways [ 14 , 15 ].”
From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [15]
Loss of p16 gene or inherited mutations within it have been frequently related to several human cancers, particularly malignant melanoma.
“This crucial role is evident from the fact that loss of the p16INK4A gene or inherited mutations within it have been frequently related to several human cancers particularly malignant melanoma (Gil and Peters, 2006; Kim and Sharpless, 2006; Li et al., 2011).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Gil and Peters, 2006
Epigenetic regulation of INK4/ARF locus is not limited to polycomb proteins; other epigenetic regulators such as ZRF, MLL1 or JMJD3 are also involved.
“Epigenetic regulation of the INK4/ARF locus is not limited to polycomb proteins as other epigenetic regulators such as ZRF, MLL1 or JMJD3 are also involved in its regulation (Gil and Peters, 2006; Agger et al., 2009; Barradas et al., 2009; Kotake et al., 2009; Ribeiro et al., 2013).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Gil and Peters, 2006
INK4/ARF locus encodes three tumor suppressors: p16 and p14ARF encoded by CDKN2A gene and p15 by CDKN2B gene.
“INK4/ARF locus encodes three tumor suppressors namely p16INK4A and p14ARF encoded by CDKN2A gene and p15INK4B by CDKN2B gene (Sharpless, 2005; Gil and Peters, 2006).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Gil and Peters, 2006
p14ARF establishes cross talk between p53 and pRB pathways by regulating stability of p53 by binding to and inhibiting MDM2, responsible for its proteasome-mediated degradation.
“In contrast, p14ARF establishes cross talk between the p53 and pRB pathways by regulating the stability of p53 by binding to and inhibiting MDM2, responsible for its proteasome-mediated degradation (Gil and Peters, 2006; Kim and Sharpless, 2006).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Gil and Peters, 2006

1 retracted

Oncogenic activity of Cdc6 through repression of the INK4/ARF locus
González, S., Klatt, P., Delgado, S., Conde, E., López‐Ríos, F., Sánchez‐Céspedes, M., Méndez, J., Antequera, F., & Serrano, M. (2006) · Nature · doi:10.1038/nature04585 · Cited by 186 · see citing works
Retracted
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.041 · Cited by 5,361 · see citing works
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 1× · see citing works
“Importantly, oncogenic signalling can elicit a senescence-like arrest that is attributable to effects on the INK4b–ARF–INK4a locus, whether direct or indirec”
Background
Proliferation, cell cycle and apoptosis in cancer
Evan, G. I., & Vousden, K. H. (2001) · Nature · doi:10.1038/35077213 · Cited by 3,383 · see citing works
Induction of apoptosis in fibroblasts by c-myc protein
Evan, G. I., Wyllie, A. H., Gilbert, C. S., Littlewood, T. D., Land, H., Brooks, M. W., Waters, C. M., Penn, L. Z., & Hancock, D. C. (1992) · Cell · doi:10.1016/0092-8674(92)90123-t · Cited by 2,941 · see citing works
A cell cycle regulator potentially involved in genesis of many tumor types
Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Liu, Q., Harshman, K., Tavtigian, S. V., Stockert, E., Day, R. S., Johnson, B. E., & Skolnick, M. H. (1994) · Science · doi:10.1126/science.8153634 · Cited by 2,751 · see citing works
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Boyer, L. A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L. A., Lee, T. I., Levine, S. S., Wernig, M., Tajonar, A., Ray, M. K., et al. (2006) · Nature · doi:10.1038/nature04733 · Cited by 2,518 · see citing works
Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
Control of Developmental Regulators by Polycomb in Human Embryonic Stem Cells
Lee, T. I., Jenner, R. G., Boyer, L. A., Guenther, M. G., Levine, S. S., Kumar, R., Chevalier, B. S., Johnstone, S. E., Cole, M. F., Isono, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.02.043 · Cited by 2,267 · see citing works
The Polycomb group protein EZH2 directly controls DNA methylation
Viré, E., Brenner, C., Deplus, R., Blanchon, L., Fraga, M., Didelot, C., Morey, L., Van Eynde, A., Bernard, D., Vanderwinden, J.-M., et al. (2006) · Nature · doi:10.1038/nature04431 · Cited by 2,204 · see citing works
BRAFE600-associated senescence-like cell cycle arrest of human naevi
Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works
pl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest
Hannon, G. J., & Beach, D. (1994) · Nature · doi:10.1038/371257a0 · Cited by 1,950 · see citing works
Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
Park, I.-K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., Morrison, S. J., & Clarke, M. F. (2003) · Nature · doi:10.1038/nature01587 · Cited by 1,871 · see citing works
Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers
Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., & Carson, D. A. (1994) · Nature · doi:10.1038/368753a0 · Cited by 1,742 · see citing works
The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580 · see citing works
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest
Ouelle, D. E., Zindy, F., Ashmun, R. A., & Sherr, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90214-7 · Cited by 1,485 · see citing works
Senescence in premalignant tumours
Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., Benguría, A., Zaballos, A., Flores, J. M., Barbacid, M., et al. (2005) · Nature · doi:10.1038/436642a · Cited by 1,482 · see citing works
Self-citation
Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells.
Lessard, J., & Sauvageau, G. (2003) · Nature · doi:10.1038/nature01572 · Cited by 1,452 · see citing works
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362 · see citing works
Telomere Shortening Triggers Senescence of Human Cells through a Pathway Involving ATM, p53, and p21CIP1, but Not p16INK4a
Herbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · see citing works
The complexity of p53 modulation: emerging patterns from divergent signalsPreprint
Giaccia, A. J., & Kastan, M. B. (1998) · Genes & Development · doi:10.1101/gad.12.19.2973 · Cited by 1,303 · see citing works
Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation
Molofsky, A. V., Pardal, R., Iwashita, T., Park, I.-K., Clarke, M. F., & Morrison, S. J. (2003) · Nature · doi:10.1038/nature02060 · Cited by 1,301 · see citing works
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsPreprint
Bracken, A. P., Dietrich, N., Pasini, D., Hansen, K. H., & Helin, K. (2006) · Genes & Development · doi:10.1101/gad.381706 · Cited by 1,258 · see citing works
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
Zindy, F., Eischen, C. M., Randle, D. H., Kamijo, T., Cleveland, J. L., Sherr, C. J., & Roussel, M. F. (1998) · Genes & Development · doi:10.1101/gad.12.15.2424 · Cited by 1,245 · see citing works
The Pezcoller lecture: cancer cell cycles revisited.
Sherr, C. J. (2000) · PubMed · Cited by 1,193 · see citing works
The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2
Stott, F. J., Bates, S., James, M. C., McConnell, B. B., Starborg, M., Brookes, S., Palmero, I., Ryan, K. M., Hara, E., Vousden, K. H., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5001 · Cited by 1,165 · see citing works
Self-citation
Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARFPreprint
Jacobs, J. J. L., Scheijen, B., Voncken, J. W., Kieboom, K., Berns, A. J. M., & van Lohuizen, M. (1999) · Genes & Development · doi:10.1101/gad.13.20.2678 · Cited by 1,060 · see citing works
Regulation of HP1–chromatin binding by histone H3 methylation and phosphorylation
Fischle, W., Tseng, B. S., Dormann, H. L., Ueberheide, B. M., Garcia, B. A., Shabanowitz, J., Hunt, D. F., Funabiki, H., & Allis, C. D. (2005) · Nature · doi:10.1038/nature04219 · Cited by 996 · see citing works
Signaling to Chromatin through Histone Modifications
Cheung, P., Allis, C. D., & Sassone-Corsi, P. (2000) · Cell · doi:10.1016/s0092-8674(00)00118-5 · Cited by 989 · see citing works
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945 · see citing works
The p16INK4a/CDKN2A tumor suppressor and its relatives
Ruas, M., & Peters, G. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(98)00017-1 · Cited by 911 · see citing works
Self-citation
Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
Kamijo, T., Weber, J. D., Zambetti, G., Zindy, F., Roussel, M. F., & Sherr, C. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8292 · Cited by 899 · see citing works
c-Myc Can Induce DNA Damage, Increase Reactive Oxygen Species, and Mitigate p53 Function
Vafa, O., Wade, M., Kern, S., Beeche, M., Pandita, T. K., Hampton, G. M., & Wahl, G. M. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00520-8 · Cited by 876 · see citing works
Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
Sharpless, N. E., Bardeesy, N., Lee, K.-H., Carrasco, D., Castrillon, D. H., Aguirre, A. J., Wu, E. A., Horner, J. W., & DePinho, R. A. (2001) · Nature · doi:10.1038/35092592 · Cited by 848 · see citing works
Senescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826 · see citing works
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819 · see citing works
Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene.Preprint
van der Lugt, N. M. T., Domen, J., Linders, K., van ROON, M. A., Robanus-Maandag, E. C., Riele, H. T., van der Valk, M., Deschamps, J., Sofroniew, M. V., & van Lohuizen, M. (1994) · Genes & Development · doi:10.1101/gad.8.7.757 · Cited by 781 · see citing works
Cyclin D-dependent kinases, INK4 inhibitors and cancer
Ortega, S., Malumbres, M., & Barbacid, M. (2002) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(02)00037-9 · Cited by 774 · see citing works
Identification of cooperating oncogenes in Eμ-myc transgenic mice by provirus tagging
van Lohuizen, M., Verbeek, S. J., Scheljen, B., Wientjens, E., van der Guidon, H., & Berns, A. J. M. (1991) · Cell · doi:10.1016/0092-8674(91)90382-9 · Cited by 762 · see citing works
The p53–Mdm2 module and the ubiquitin system
Michael, D., & Oren, M. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00099-8 · Cited by 759 · see citing works
Mechanisms of cyclin-dependent kinase regulation: structures of cdks, their cyclin activators, and cip and INK4 inhibitors
Pavletich, N. P. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2640 · Cited by 746 · see citing works
Stem Cells and Cancer
Valk-Lingbeek, M. E., Bruggeman, S. W. M., & van Lohuizen, M. (2004) · Cell · doi:10.1016/j.cell.2004.08.005 · Cited by 743 · see citing works
Regulation of p16 CDKN2 Expression and Its Implications for Cell Immortalization and Senescence
Hara, E., Smith, R., Parry, D., Tahara, H., Stone, S., & Peters, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.859 · Cited by 733 · see citing works
Self-citation
Tumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · see citing works
Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin
Hirota, T., Lipp, J., Toh, B., & Peters, J. (2005) · Nature · doi:10.1038/nature04254 · Cited by 662 · see citing works
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence
Ohtani, N., Zebedee, Z., Huot, T. J. G., Stinson, J. A., Sugimoto, M., Ohashi, Y., Sharrocks, A. D., Peters, G., & Hara, E. (2001) · Nature · doi:10.1038/35059131 · Cited by 654 · see citing works
Self-citation
Binary switches and modification cassettes in histone biology and beyond
Fischle, W., Wang, Y., & Allis, C. D. (2003) · Nature · doi:10.1038/nature02017 · Cited by 627 · see citing works
p19ARF links the tumour suppressor p53 to Ras
Palmero, I., Pantoja, C., & Serrano, M. (1998) · Nature · doi:10.1038/25870 · Cited by 617 · see citing works
E1A signaling to p53 involves the p19ARFtumor suppressorPreprint
de Stanchina, E., McCurrach, M. E., Zindy, F., Shieh, S.-Y., Ferbeyre, G., Samuelson, A. V., Prives, C. L., Roussel, M. F., Sherr, C. J., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.15.2434 · Cited by 607 · see citing works
Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathwaysPreprint
Molofsky, A. V., He, S., Bydon, M., Morrison, S. J., & Pardal, R. (2005) · Genes & Development · doi:10.1101/gad.1299505 · Cited by 586 · see citing works
Repression of p15INK4b expression by Myc through association with Miz-1
Staller, P., Peukert, K., Kiermaier, A. C., Seoane, J., Lukas, J., Karsunky, H., Möröy, T., Bártek, J., Massagué, J., Hänel, F., et al. (2001) · Nature Cell Biology · doi:10.1038/35070076 · Cited by 574 · see citing works
Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging
Zindy, F., Quelle, D. E., Roussel, M. F., & Sherr, C. J. (1997) · Oncogene · doi:10.1038/sj.onc.1201178 · Cited by 574 · see citing works
Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice
Krimpenfort, P., Quon, K. C., Mooi, W. J., Loonstra, A., & Berns, A. (2001) · Nature · doi:10.1038/35092584 · Cited by 568 · see citing works
Comparative biology of mouse versus human cells: modelling human cancer in mice
Rangarajan, A., & Weinberg, R. A. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1235 · Cited by 567 · see citing works
Species- and cell type-specific requirements for cellular transformation
Rangarajan, A., Hong, S. J., Gifford, A., & Weinberg, R. A. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.009 · Cited by 555 · see citing works
Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas
Leung, C., Lingbeek, M., Shakhova, O., Liu, J. K., Tanger, E., Saremaslani, P., van Lohuizen, M., & Marino, S. (2004) · Nature · doi:10.1038/nature02385 · Cited by 541 · see citing works
PML is induced by oncogenic ras and promotes premature senescence
Ferbeyre, G., de Stanchina, E., Querido, E., Baptiste, N., Prives, C., & Lowe, S. W. (2000) · Genes & Development · doi:10.1101/gad.14.16.2015 · Cited by 536 · see citing works
twist is a potential oncogene that inhibits apoptosis
Maestro, R., Tos, A. P. D., Hamamori, Y., Krasnokutsky, S., Sartorelli, V., Kedes, L., Doglioni, C., Beach, D. H., & Hannon, G. J. (1999) · Genes & Development · doi:10.1101/gad.13.17.2207 · Cited by 516 · see citing works
Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in Eμ-myc transgenic mice
Haupt, Y., Alexander, W. S., Barri, G., Klinken, S. P., & Adams, J. M. (1991) · Cell · doi:10.1016/0092-8674(91)90383-a · Cited by 513 · see citing works
TGFβ influences Myc, Miz-1 and Smad to control the CDK inhibitor p15INK4b
Seoane, J., Pouponnot, C., Staller, P., Schader, M. B., Eilers, M., & Massagué, J. (2001) · Nature Cell Biology · doi:10.1038/35070086 · Cited by 489 · see citing works
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482 · cited 1× · see citing works
“The same selectivity applies to the upregulation of INK4a in cells that express a dominant-negative version of the telomeric repeat-binding protein TRF2 (Ref”
Background
Identification of CDK4 as a target of c-MYC
Hermeking, H., Rago, C., Schuhmacher, M., Li, Q., Barrett, J. F., Obaya, Á. J., O’Connell, B. C., Mateyak, M. K., Tam, W., Kohlhuber, F., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050586197 · Cited by 471 · see citing works
INK4a/ARF: A multifunctional tumor suppressor locus
Sharpless, N. E. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.08.021 · Cited by 442 · see citing works
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438 · see citing works
Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK–mediated activation of the p16Ink4a-p19Arf pathway
Bulavin, D. V., Dudgeon, C., Nannenga, B., Timofeev, O. N., Donehower, L. A., Anderson, C. W., Appella, E., & Fornace, A. J. (2004) · Nature Genetics · doi:10.1038/ng1317 · Cited by 410 · see citing works
Deletion of p16 and p15 genes in brain tumors.
Jen, J., Harper, J. W., Bigner, S. H., Bigner, D. D., Papadopoulos, N., Markowitz, S. D., Willson, J. K. V., Kinzler, K. W., & Vogelstein, B. (1994) · PubMed · Cited by 404 · see citing works
The power and the promise of oncogene-induced senescence markers
Collado, M., & Serrano, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1884 · Cited by 404 · see citing works
Role of the proto-oncogene Pokemon in cellular transformation and ARF repression
Maeda, T., Hobbs, R. M., Merghoub, T., Guernah, I., Zelent, A., Cordon‐Cardo, C., Teruya‐Feldstein, J., & Pandolfi, P. P. (2005) · Nature · doi:10.1038/nature03203 · Cited by 399 · see citing works
Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression
Carreira, S., GOODALL, J. C., Aksan, I., Rocca, S. A. L., Galibert, M., Denat, L., Larue, L., & Goding, C. R. (2005) · Nature · doi:10.1038/nature03269 · Cited by 395 · see citing works
Mitogen‐activated protein kinase p38 defines the common senescence‐signalling pathway
Iwasa, H., Han, J., & Ishikawa, F. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00620.x · Cited by 388 · see citing works
Complex structure and regulation of the P16 (MTS1) locus.
Stone, S., Jiang, P., Dayananth, P., Tavtigian, S. V., Katcher, H. L., Parry, D., Peters, G., & Kamb, A. (1995) · PubMed · Cited by 383 · see citing works
Self-citation
Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster
Tolhuis, B., Muijrers, I., de Wit, E., Teunissen, H., Talhout, W., van Steensel, B., & van Lohuizen, M. (2006) · Nature Genetics · doi:10.1038/ng1792 · Cited by 380 · see citing works
Sequential Activation of the MEK-Extracellular Signal-Regulated Kinase and MKK3/6-p38 Mitogen-Activated Protein Kinase Pathways Mediates Oncogenic ras -Induced Premature Senescence
Wang, W., Chen, J. X., Liao, R., Deng, Q., Zhou, J. J., Huang, S., & Sun, P. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.10.3389-3403.2002 · Cited by 376 · see citing works
Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers
Jacobs, J. J. L., Keblusek, P., Robanus-Maandag, E., Kristel, P., Lingbeek, M., Nederlof, P. M., van Welsem, T., van de Vijver, M. J., Koh, E. Y., Daley, G. Q., et al. (2000) · Nature Genetics · doi:10.1038/81583 · Cited by 368 · see citing works
DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation
Raveh, T., Droguett, G., Horwitz, M. S., DePinho, R. A., & Kimchi, A. (2001) · Nature Cell Biology · doi:10.1038/35050500 · Cited by 361 · see citing works
Historical claims and current interpretations of replicative aging
Wright, W. E., & Shay, J. W. (2002) · Nature Biotechnology · doi:10.1038/nbt0702-682 · Cited by 355 · see citing works
The Human ARF Cell Cycle Regulatory Gene Promoter Is a CpG Island Which Can Be Silenced by DNA Methylation and Down-Regulated by Wild-Type p53
Robertson, K. D., & Jones, P. A. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.11.6457 · Cited by 352 · see citing works
Rnf2 ( Ring1b ) deficiency causes gastrulation arrest and cell cycle inhibition
Voncken, J. W., Roelen, B. A. J., Roefs, M., de Vries, S., Verhoeven, E., Marino, S., Deschamps, J., & van Lohuizen, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0434312100 · Cited by 343 · see citing works
Polycomb CBX7 has a unifying role in cellular lifespan.
Gil, J., Bernard, D., Martínez, D., & Beach, D. (2004) · Nature Cell Biology · doi:10.1038/ncb1077 · Cited by 341 · see citing works
Self-citation
JunB suppresses cell proliferation by transcriptional activation of p16INK4a expression
Passegue, E. A., & Wagner, E. F. (2000) · The EMBO Journal · doi:10.1093/emboj/19.12.2969 · Cited by 333 · see citing works
Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5
Roberts, C. W. M., Leroux, M. M., Fleming, M. D., & Orkin, S. H. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00185-x · Cited by 333 · see citing works
c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points
Mateyak, M. K., Obaya, Á. J., & Sedivy, J. M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.7.4672 · Cited by 331 · see citing works
A novel p16INK4A transcript.
Mao, L., Merlo, A. U., Bedi, G. C., Shapiro, G. I., Edwards, C. D., Rollins, B. J., & Sidransky, D. (1995) · PubMed · Cited by 329 · see citing works
Polycomb complexes and silencing mechanisms
Lund, A. H., & van Lohuizen, M. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.03.010 · Cited by 316 · see citing works
Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice
Bruggeman, S. W. M., Valk-Lingbeek, M. E., van der Stoop, P. P. M., Jacobs, J. J. L., Kieboom, K., Tanger, E., Hulsman, D., Leung, C., Arsenijevic, Y., Marino, S., et al. (2005) · Genes & Development · doi:10.1101/gad.1299305 · Cited by 315 · see citing works
JunD Protects Cells from p53-Dependent Senescence and Apoptosis
Weitzman, J. B., Fiette, L., Matsuo, K., & Yaniv, M. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00109-x · Cited by 269 · see citing works
MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A
Loercher, A. E., Tank, E. M. H., Delston, R. B., & Harbour, J. W. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200410115 · Cited by 266 · see citing works
Limited overlapping roles of P15INK4b and P18INK4c cell cycle inhibitors in proliferation and tumorigenesis
Latres, E., Malumbres, M., Sotillo, R., Martín, J., Ortega, S., Martín‐Caballero, J., Flores, J. M., Cordón‐Cardo, C., & Barbacid, M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3496 · Cited by 257 · see citing works
The t(8;21) fusion protein, AML1–ETO, specifically represses the transcription of the p14ARF tumor suppressor in acute myeloid leukemia
Linggi, B. E., Müller‐Tidow, C., van de Locht, L. T., Hu, M., Nip, J., Serve, H. L., Berdel, W. E., van der Reijden, B., Quelle, D. E., Rowley, J. D., et al. (2002) · Nature Medicine · doi:10.1038/nm726 · Cited by 256 · see citing works
Chromosomal Distribution of PcG Proteins during Drosophila Development
Negre, N. N., Hennetin, J., Sun, L. V., Lavrov, S. A., Bellis, M., White, K. P., & Cavalli, G. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040170 · Cited by 246 · see citing works
Significant Role for p16INK4a in p53-Independent Telomere-Directed Senescence
Jacobs, J. J. L., & de Lange, T. (2004) · Current Biology · doi:10.1016/j.cub.2004.12.025 · Cited by 237 · cited 1× · see citing works
“However, opinions are divided on whether and how INK4a is activated by telomere loss or other forms of DNA damag”
Background
Myc Downregulation by Transforming Growth Factor β Required for Activation of the p15Ink4b G1 Arrest Pathway
Warner, B. J., Blain, S. W., Seoane, J., & Massagué, J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.5913 · Cited by 230 · see citing works
Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a
Alani, R. M., Young, A. Z., & Shifflett, C. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141235398 · Cited by 227 · see citing works
The differential impact of p16INK4a or p19ARF deficiency on cell growth and tumorigenesis
Sharpless, N. E., Ramsey, M. R., Balasubramanian, P., Castrillon, D. H., & DePinho, R. A. (2004) · Oncogene · doi:10.1038/sj.onc.1207074 · Cited by 224 · see citing works
INK4a‐deficient human diploid fibroblasts are resistant to RAS‐induced senescence
Brookes, S., Rowe, J., Ruas, M., Llanos, S., Clark, P. A., Lomax, M., James, M. C., Vatcheva, R., Bates, S., Vousden, K. H., et al. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf289 · Cited by 220 · see citing works
Self-citation
Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16 INK4a but not by the alternative reading frame protein p19 ARF
Quelle, D. E., Cheng, M. M., Ashmun, R. A., & Sherr, C. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.669 · Cited by 217 · see citing works
Role of p14ARF in Replicative and Induced Senescence of Human Fibroblasts
Wei, W., Hemmer, R. M., & Sedivy, J. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6748-6757.2001 · Cited by 217 · see citing works
p19ARF directly and differentially controls the functions of c-Myc independently of p53
Qi, Y., Gregory, M. A., Li, Z., Brousal, J. P., West, K. A., & Hann, S. (2004) · Nature · doi:10.1038/nature02958 · Cited by 214 · see citing works
Oncogenic ras activates the ARF-p53 pathway to suppress epithelial cell transformation
Lin, A. W., & Lowe, S. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091100298 · Cited by 213 · see citing works
Re-expression of hSNF5/INI1/BAF47 in pediatric tumor cells leads to G1arrest associated with induction of p16ink4a and activation of RB
Betz, B. L., Strobeck, M. W., Reisman, D., Knudsen, E. S., & Weissman, B. E. (2002) · Oncogene · doi:10.1038/sj.onc.1205706 · Cited by 212 · see citing works
Deregulated β‐catenin induces a p53‐ and ARF‐dependent growth arrest and cooperates with Ras in transformation
Damalas, A., Kahan, S., Shtutman, M. S., Ben‐Ze'ev, A., & Oren, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.17.4912 · Cited by 206 · see citing works
Cyclin E and c‐Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins
Alevizopoulos, K., Vlach, J., Hennecke, S., & Amati, B. B. (1997) · The EMBO Journal · doi:10.1093/emboj/16.17.5322 · Cited by 202 · see citing works
High Intensity ras Signaling Induces Premature Senescence by Activating p38 Pathway in Primary Human Fibroblasts*
Deng, Q.-D., Liao, R., Wu, B.-L., & Sun, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308644200 · Cited by 188 · see citing works
Growth retardation and premature aging phenotypes in mice with disruption of the SNF2-like gene, PASGPreprint
Sun, L.-Q., Lee, D. W., Zhang, Q., Xiao, W., Raabe, E. H., Meeker, A. K., Miao, D., Huso, D. L., & Arceci, R. J. (2004) · Genes & Development · doi:10.1101/gad.1176104 · Cited by 182 · see citing works
Werner syndrome protein limits MYC-induced cellular senescencePreprint
Grandori, C., Wu, K.-J., Fernandez, P. C., Ngouenet, C., Grim, J. A., Clurman, B. E., Moser, M. J., Oshima, J., Russell, D. W., Swisshelm, K. L., et al. (2003) · Genes & Development · doi:10.1101/gad.1100303 · Cited by 182 · see citing works
Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16 INK4a
Guney, I., Wu, S., & Sedivy, J. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600069103 · Cited by 180 · see citing works
Computer-assisted identification of cell cycle-related genes: new targets for E2F transcription factors
Kel, A. E., Kel-Margoulis, O. V., Farnham, P., Bartley, S. M., Wingender, E., & Zhang, M. Q. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4650 · Cited by 175 · see citing works
Gene repression by Polycomb group protein complexes: a distinct complex for every occasion?
Otte, A. P., & Kwaks, T. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(03)00108-4 · Cited by 172 · see citing works
Repression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kineticsPreprint
Aslanian, A., Iaquinta, P. J., Verona, R. I., & Lees, J. A. (2004) · Genes & Development · doi:10.1101/gad.1196704 · Cited by 170 · see citing works
Association of BMI1 with Polycomb Bodies Is Dynamic and Requires PRC2/EZH2 and the Maintenance DNA Methyltransferase DNMT1
Hernández‐Muñoz, I., Taghavi, P., Kuijl, C. P., Neefjes, J., & van Lohuizen, M. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.11047-11058.2005 · Cited by 168 · see citing works
MAPKAP Kinase 3pK Phosphorylates and Regulates Chromatin Association of the Polycomb Group Protein Bmi1
Voncken, J. W., Niessen, H. E. C., Neufeld, B., Rennefahrt, U. E. E., Dahlmans, V. E. H., Kubben, N., Holzer, B., Ludwig, S., & Rapp, U. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407155200 · Cited by 166 · see citing works
p16 Is Required for hSNF5 Chromatin Remodeler-induced Cellular Senescence in Malignant Rhabdoid Tumor Cells
Oruetxebarria, I., Venturini, F., Kekarainen, T., Houweling, A., Zuijderduijn, L. M. P., Mohd-Sarip, A., Vries, R. G. J., Hoeben, R. C., & Verrijzer, C. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309333200 · Cited by 160 · see citing works
The T-box Repressors TBX2 and TBX3Specifically Regulate the Tumor Suppressor Genep14 via a Variant T-site in the Initiator
Lingbeek, M. E., Jacobs, J. J. L., & van Lohuizen, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200403200 · Cited by 160 · see citing works
TBX-3, the Gene Mutated in Ulnar-Mammary Syndrome, Is a Negative Regulator of p19 and Inhibits Senescence
Brummelkamp, T. R., Kortlever, R. M., Lingbeek, M., Trettel, F., MacDonald, M. E., van Lohuizen, M., & Bernards, R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110492200 · Cited by 154 · see citing works
Cellular Response to Oncogenic Ras Involves Induction of the Cdk4 and Cdk6 Inhibitor p15INK4b
Malumbres, M., de Castro, I. P., Hernández, M. I., Jiménez, M., Corral, T., & Pellicer, À. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2915-2925.2000 · Cited by 154 · see citing works
Arf tumor suppressor promoter monitors latent oncogenic signals in vivo
Zindy, F., Williams, R. T., Baudino, T. A., Rehg, J. E., Skapek, S. X., Cleveland, J. L., Roussel, M. F., & Sherr, C. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2536808100 · Cited by 150 · see citing works
Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1
Inoue, K., Roussel, M. F., & Sherr, C. J. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3993 · Cited by 144 · see citing works
Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescence.
Haq, R., Brenton, J. D., Takahashi, M. T., Finan, D., Finkielsztein, A., Damaraju, S., Rottapel, R. K., & Zanke, B. W. (2002) · PubMed · Cited by 143 · see citing works
Overexpression of MYC causes p53 -dependent G 2 arrest of normal fibroblasts
Felsher, D. W., Zetterberg, A., Zhu, J., Tlsty, T. D., & Bishop, J. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190327097 · Cited by 137 · see citing works
Mammalian Polyhomeotic Homologues Phc2 and Phc1 Act in Synergy To Mediate Polycomb Repression of Hox Genes
Isono, K., Fujimura, Y., Shinga, J., Yamaki, M., Wang, J. O., Takihara, Y., Murahashi, Y., Takada, Y., Mizutani-Koseki, Y., & Koseki, H. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.15.6694-6706.2005 · Cited by 136 · see citing works
Accumulation of p16INK4a in mouse fibroblasts as a function of replicative senescence and not of retinoblastoma gene status
Palmero, I., McConnell, B. B., Parry, D., Brookes, S., Hara, E., Bates, S., Jat, P., & Peters, G. G. (1997) · Oncogene · doi:10.1038/sj.onc.1201212 · Cited by 123 · see citing works
Self-citation
Defining the molecular basis of Arf and Hdm2 interactions
Bothner, B. B., Lewis, W. S., DiGiammarino, E. L., Weber, J. D., Bothner, S. J., & Kriwacki, R. W. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5110 · Cited by 122 · see citing works
Ras-Raf-Arf Signaling Critically Depends on the Dmp1 Transcription Factor
Sreeramaneni, R., Chaudhry, A., McMahon, M., Sherr, C. J., & Inoue, K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.220-232.2005 · Cited by 121 · see citing works
The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development
McKeller, R. N., Fowler, J. L., Cunningham, J. J., Warner, N., Smeyne, R. J., Zindy, F., & Skapek, S. X. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052484199 · Cited by 118 · see citing works
Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence.
Krones-Herzig, A., Adamson, E., & Mercola, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2628034100 · Cited by 118 · see citing works
Loss of the ARF tumor suppressor reverses premature replicative arrest but not radiation hypersensitivity arising from disabled atm function.
Kamijo, T., van de Kamp, E. H., Chong, M. J., Zindy, F., Diehl, J. A., Sherr, C. J., & McKinnon, P. J. (1999) · PubMed · Cited by 117 · see citing works
Myc-ARF (Alternate Reading Frame) Interaction Inhibits the Functions of Myc
Datta, A., Nag, A., Pan, W., Hay, N., Gartel, A. L., Colamonici, O. R., Mori, Y., & Raychaudhuri, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312305200 · Cited by 112 · see citing works
Differential effects of p19 Arf and p16 Ink4a loss on senescence of murine bone marrow-derived preB cells and macrophages
Randle, D. H., Zindy, F., Sherr, C. J., & Roussel, M. F. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171217498 · Cited by 108 · see citing works
Epstein-Barr virus LMP1 blocks p16INK4a–RB pathway by promoting nuclear export of E2F4/5
Ohtani, N., Brennan, P., Gaubatz, S., Sanij, E., Hertzog, P. J., Wolvetang, E. J., Ghysdael, J., Rowe, M., & Hara, E. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302085 · Cited by 103 · see citing works
Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes
Drayton, S., Rowe, J., Jones, R., Vatcheva, R., Heavens, D., Marshall, J. F., Fried, M., & Peters, G. G. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00242-3 · Cited by 94 · see citing works
Self-citation
Oncogenic Ras Induces p19ARF and Growth Arrest in Mouse Embryo Fibroblasts Lacking p21Cip1 and p27Kip1 without Activating Cyclin D-dependent Kinases
Groth, A., Weber, J. D., Willumsen, B. M., Sherr, C. J., & Roussel, M. F. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003417200 · Cited by 92 · see citing works
Bmi-1 Regulation of INK4A-ARF Is a Downstream Requirement for Transformation of Hematopoietic Progenitors by E2a-Pbx1
Smith, K. S., Chanda, S. K., Lingbeek, M., Ross, D. T., Botstein, D., van Lohuizen, M., & Cleary, M. L. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00277-6 · Cited by 89 · see citing works
Transcriptional Coactivator Cited2 Induces Bmi1 and Mel18 and Controls Fibroblast Proliferation viaInk4a/ARF
Kranc, K. R., Bamforth, S. D., Bragança, J., Norbury, C. J., van Lohuizen, M., & Bhattacharya, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7658-7666.2003 · Cited by 84 · see citing works
Suppression of the p53- or pRB-mediated G1 checkpoint is required for E2F-induced S-phase entry
Lomazzi, M., Moroni, M. C., Jensen, M. R., Frittoli, E., & Helin, K. (2002) · Nature Genetics · doi:10.1038/ng891 · Cited by 83 · see citing works
Contribution of p16INK4a to replicative senescence of human fibroblasts
Brookes, S., Rowe, J., del Arroyo, A. G., BOND, J. A., & Peters, G. G. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.04.035 · Cited by 83 · see citing works
Self-citation
Distinct E2F‐mediated transcriptional program regulates p14 ARF gene expression
Komori, H., Enomoto, M., Nakamura, M., Iwanaga, R., & Ohtani, K. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600836 · Cited by 82 · see citing works
LMP1 of Epstein–Barr virus suppresses cellular senescence associated with the inhibition of p16INK4a expression
Yang, X., He, Z., Xin, B., & Cao, L. (2000) · Oncogene · doi:10.1038/sj.onc.1203515 · Cited by 71 · see citing works
Absence of p16 INK4a and truncation of ARF tumor suppressors in chickens
Kim, S.-H., Mitchell, M., Fujii, H., Llanos, S., & Peters, G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0135557100 · Cited by 63 · see citing works
Self-citation
Comparative structure and characterization of a CDKN2 gene in a Xiphophorus fish melanoma model
Kazianis, S., Morizot, D. C., Coletta, L. D., Johnston, D., Woolcock, B. W., Vielkind, J., & Nairn, R. (1999) · Oncogene · doi:10.1038/sj.onc.1202884 · Cited by 53 · see citing works
One INK4 gene and no ARF at the Fugu equivalent of the human INK4A/ARF/INK4B tumour suppressor locus
Gilley, J., & Fried, M. (2001) · Oncogene · doi:10.1038/sj.onc.1204933 · Cited by 50 · see citing works
AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene
Ameyar‐Zazoua, M., Wisniewska, M. B., Bakiri, L., Wagner, E. F., Yaniv, M., & Weitzman, J. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208424 · Cited by 40 · see citing works
Sequential extension of proliferative lifespan in human fibroblasts induced by over-expression of CDK4 or 6 and loss of p53 function
Morris, M. R., Hepburn, P. J., & Wynford‐Thomas, D. (2002) · Oncogene · doi:10.1038/sj.onc.1205492 · Cited by 37 · see citing works
Inhibition of v-Abl transformation by p53 and p19ARF
Cong, F., Zou, X., Hinrichs, K., Calame, K. L., & Goff, S. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203290 · Cited by 37 · see citing works
Disruption of E2F signaling suppresses the INK4a-induced proliferative defect in M33-deficient mice
Coré, N., Joly, F., Boned, A., & Djabali, M. (2004) · Oncogene · doi:10.1038/sj.onc.1207998 · Cited by 33 · see citing works
E2F and Ras Synergize in Transcriptionally Activating p14ARFExpression
Berkovich, E., Lamed, Y., & Ginsberg, D. (2003) · Cell Cycle · doi:10.4161/cc.2.2.293 · Cited by 33 · see citing works
Upregulation of chicken p15INK4b at senescence and in the developing brain
Kim, S., Rowe, J., Fujii, H., Jones, R., Schmierer, B., Kong, B. ‐., Kuchler, K., Foster, D. N., Ish‐Horowicz, D., & Peters, G. (2006) · Journal of Cell Science · doi:10.1242/jcs.02989 · Cited by 32 · see citing works
Self-citation
P66ShcA interacts with MAPKAP kinase 2 and regulates its activity
Yannoni, Y. M., Gaestel, M., & Lin, L. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00351-5 · Cited by 24 · see citing works
The basic helix–loop–helix transcription factor TAL1/SCL inhibits the expression of the p16INK4A and pTα genes
Hansson, A., Manetopoulos, C., Jönsson, J., & Axelson, H. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.030 · Cited by 23 · see citing works

Flagged first, then by citations

3 of the 153 references couldn’t be matched to a known paper.

Sorted by citations

Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Molecular Mechanisms of Long Noncoding RNAs
Wang, K., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.018 · Cited by 4,390 · see citing works
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · see citing works
“both of these pathways [14,15].”
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · see citing works
2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults
Greenland, P., Alpert, J. S., Beller, G. A., Benjamin, E. J., Budoff, M. J., Fayad, Z. A., Foster, E., Hlatky, M. A., Hodgson, J. M., Kushner, F. G., et al. (2010) · Circulation · doi:10.1161/cir.0b013e3182051b4c · Cited by 1,968 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a
Yap, K. L., Li, S., Muñoz-Cabello, A. M., Raguz, S., Zeng, L., Mujtaba, S., Gil, J., Walsh, M. J., & Zhou, M.-M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.03.021 · Cited by 1,391 · see citing works
Self-citation
Cyclin D as a therapeutic target in cancer
Musgrove, E. A., Caldon, C. E., Barraclough, J., Stone, A., & Sutherland, R. L. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3090 · Cited by 1,370 · see citing works
2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults
Greenland, P., Alpert, J. S., Beller, G. A., Benjamin, E. J., Budoff, M. J., Fayad, Z. A., Foster, E., Hlatky, M. A., Hodgson, J. M., Kushner, F. G., et al. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.09.001 · Cited by 1,322 · see citing works
Senescence and aging: Causes, consequences, and therapeutic avenues
McHugh, D., & Gil, J. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201708092 · Cited by 1,233 · see citing works
Self-citation
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Self-citation
The nucleolus under stress
Boulon, S., Westman, B. J., Hutten, S., Boisvert, F.-M., & Lamond, A. I. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.024 · Cited by 1,103 · see citing works
Mechanisms of long noncoding RNA function in development and disease
Schmitz, S. U., Grote, P., & Herrmann, B. G. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2174-5 · Cited by 1,088 · see citing works
p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype
Freund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · see citing works
Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene
Kotake, Y., Nakagawa, T., Kitagawa, K., Suzuki, S., Liu, N., Kitagawa, M., & Xiong, Y. (2011) · Oncogene · doi:10.1038/onc.2010.568 · Cited by 1,001 · see citing works
Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-Coding RNA Correlates with Atherosclerosis Risk
Burd, C. E., Jeck, W. R., Liu, Y., Sanoff, H. K., Wang, Z., & Sharpless, N. E. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001233 · Cited by 895 · see citing works
Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation
Orford, K. W., & Scadden, D. T. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2269 · Cited by 851 · see citing works
The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells
Bracken, A. P., Kleine-Kohlbrecher, D., Dietrich, N., Pasini, D., Gargiulo, G., Beekman, C., Theilgaard-Mönch, K., Minucci, S., Porse, B. T., Marine, J.-C., et al. (2007) · Genes & Development · doi:10.1101/gad.415507 · Cited by 850 · see citing works
Cellular senescence and tumor suppressor gene p16
Rayess, H., Wang, M. B., & Srivatsan, E. S. (2012) · International Journal of Cancer · doi:10.1002/ijc.27316 · Cited by 825 · see citing works
Polycomb Group Proteins: Multi-Faceted Regulators of Somatic Stem Cells and Cancer
Sauvageau, M., & Sauvageau, G. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.08.002 · Cited by 676 · see citing works
Long Intergenic Noncoding RNAs: New Links in Cancer Progression
Tsai, M.-C., Spitale, R. C., & Chang, H. Y. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2483 · Cited by 641 · see citing works
Senescent cells as a source of inflammatory factors for tumor progression
Davalos, A. R., Coppe, J.-P., Campisi, J., & Desprez, P.-Y. (2010) · Cancer and Metastasis Reviews · doi:10.1007/s10555-010-9220-9 · Cited by 636 · see citing works
Chronic myeloid leukaemia as a model of disease evolution in human cancer
Melo, J. V., & Barnes, D. J. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2147 · Cited by 616 · see citing works
Therapeutic Targeting of Long Non-Coding RNAs in Cancer
Arun, G., Diermeier, S. D., & Spector, D. L. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.01.001 · Cited by 612 · see citing works
Divorcing ARF and p53: an unsettled case
Sherr, C. J. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1954 · Cited by 595 · see citing works
Targetable genetic features of primary testicular and primary central nervous system lymphomas
Chapuy, B., Roemer, M. G. M., Stewart, C., Tan, Y., Abo, R., Zhang, L., Dunford, A. J., Meredith, D. M., Thorner, A. R., Jordanova, E. S., et al. (2015) · Blood · doi:10.1182/blood-2015-10-673236 · Cited by 584 · see citing works
Polycomb group proteins: navigators of lineage pathways led astray in cancer
Bracken, A. P., & Helin, K. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2736 · Cited by 562 · see citing works
EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas
Mohammad, F., Weissmann, S., Leblanc, B., Pandey, D. P., Højfeldt, J. W., Comet, I., Zheng, C., Johansen, J. V., Rapin, N., Porse, B. T., et al. (2017) · Nature Medicine · doi:10.1038/nm.4293 · Cited by 535 · see citing works
Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases
Hydbring, P., Malumbres, M., & Sicinski, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.27 · Cited by 528 · see citing works
The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivoPreprint
Huse, J. T., Brennan, C., Hambardzumyan, D., Wee, B., Pena, J., Rouhanifard, S. H., Sohn-Lee, C., le Sage, C., Agami, R., Tuschl, T., et al. (2009) · Genes & Development · doi:10.1101/gad.1777409 · Cited by 511 · see citing works
p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors
Romagosa, C., Simonetti, S., López-Vicente, L., Mazo, A., Lleonart, M. E., Castellvi, J., & Ramon y Cajal, S. (2011) · Oncogene · doi:10.1038/onc.2010.614 · Cited by 509 · see citing works
Tumor Suppressor and Aging Biomarker p16INK4a Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype
Coppé, J.-P., Rodier, F., Patil, C. K., Freund, A., Desprez, P.-Y., & Campisi, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.257071 · Cited by 506 · see citing works
ANRIL Expression Is Associated With Atherosclerosis Risk at Chromosome 9p21
Holdt, L. M., Beutner, F., Scholz, M. R., Gielen, S., Gäbel, G., Bergert, H., Schuler, G. C., Thiery, J., & Teupser, D. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.196832 · Cited by 452 · see citing works
Protein tyrosine phosphatases – from housekeeping enzymes to master regulators of signal transduction
Tonks, N. K. (2012) · FEBS Journal · doi:10.1111/febs.12077 · Cited by 438 · see citing works
The Causes and Consequences of Polyploidy in Normal Development and Cancer
Davoli, T., & de Lange, T. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154234 · Cited by 432 · see citing works
The H3K27me3 demethylase JMJD3 contributes to the activation of theINK4A–ARFlocus in response to oncogene- and stress-induced senescence
Agger, K., Cloos, P. A. C., Rudkjær, L., Williams, K., Andersen, G., Christensen, J., & Helin, K. (2009) · Genes & Development · doi:10.1101/gad.510809 · Cited by 427 · see citing works
Implications of Genetic and Epigenetic Alterations of CDKN2A (p16 INK4a ) in Cancer
Zhao, R., Choi, B. Y., Lee, M.-H., Bode, A. M., & Dong, Z. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.04.017 · Cited by 425 · see citing works
Cellular senescence: a link between cancer and age-related degenerative disease?
Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.09.001 · Cited by 421 · see citing works
Epigenetics and cardiovascular disease
Ordovás, J., & Smith, C. E. (2010) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2010.104 · Cited by 452 · see citing works
Biomarkers of aging
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression
Cunnington, M. S., Santibanez‐Koref, M., Mayosi, B. M., Burn, J., & Keavney, B. D. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000899 · Cited by 379 · see citing works
Cis-acting noncoding RNAs: friends and foes
Guil, S., & Esteller, M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2428 · Cited by 369 · see citing works
Translational Control in Cancer EtiologyPreprint
Ruggero, D. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012336 · Cited by 362 · see citing works
Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS
Barradas, M., Anderton, E., Acosta, J. C., Li, S., Banito, A., Rodriguez-Niedenführ, M., Maertens, G., Banck, M., Zhou, M.-M., Walsh, M. J., et al. (2009) · Genes & Development · doi:10.1101/gad.511109 · Cited by 352 · see citing works
Self-citation
Cellular senescence and organismal aging
Jeyapalan, J. C., & Sedivy, J. M. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.04.001 · Cited by 347 · see citing works
The Mdm2–p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor
Manfredi, J. J. (2010) · Genes & Development · doi:10.1101/gad.1941710 · Cited by 344 · see citing works
Tailoring to RB: tumour suppressor status and therapeutic response
Knudsen, E. S., & Knudsen, K. E. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2401 · Cited by 345 · see citing works
Breed-Predispositions to Cancer in Pedigree Dogs
Dobson, J. M. (2013) · ISRN Veterinary Science · doi:10.1155/2013/941275 · Cited by 340 · see citing works
Regulatory Mechanisms of Tumor Suppressor P16INK4Aand Their Relevance to Cancer
Li, J., Poi, M. J., & Tsai, M. (2011) · Biochemistry · doi:10.1021/bi200642e · Cited by 336 · see citing works
Genetic variants at the 9p21 locus contribute to atherosclerosis through modulation of ANRIL and CDKN2A/B
Congrains, A., Kamide, K., Oguro, R., Yasuda, O., Miyata, K., Yamamoto, E., Kawai, T., Kusunoki, H., Yamamoto, H., Takeya, Y., et al. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.11.017 · Cited by 330 · see citing works
Skin Aging, Cellular Senescence and Natural Polyphenols
Csekes, E., & Račková, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312641 · Cited by 334 · see citing works
INK4 proteins, a family of mammalian CDK inhibitors with novel biological functions
Cánepa, E. T., Scassa, M. É., Ceruti, J. M., Marazita, M. C., Carcagno, A. L., Sirkin, P. F., & Ogara, M. F. (2007) · IUBMB Life · doi:10.1080/15216540701488358 · Cited by 314 · see citing works
Neighboring Gene Regulation by Antisense Long Non-Coding RNAs
Villegas, V. E., & Zaphiropoulos, P. G. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16023251 · Cited by 309 · see citing works
Histone methyltransferases in cancer
Albert, M., & Helin, K. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.10.007 · Cited by 312 · see citing works
Zeb1 links epithelial-mesenchymal transition and cellular senescence
Liu, Y., El‐Naggar, S., Darling, D. S., Higashi, Y., & Dean, D. C. (2008) · Development · doi:10.1242/dev.007047 · Cited by 304 · see citing works
Senescence from G2 arrest, revisited
Gire, V., & Dulić, V. (2015) · Cell Cycle · doi:10.1080/15384101.2014.1000134 · Cited by 300 · see citing works
The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p
Xu, M., Chen, X., Kang, L., Zeng, K., Liu, X., Pan, B., Xu, X., Xu, T., Hu, X., Sun, L., et al. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0894-x · Cited by 304 · see citing works
The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15Ink4b
He, J., Kallin, E. M., Tsukada, Y.-I., & Zhang, Y. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1499 · Cited by 295 · see citing works
Mesenchymal Stem/Stromal Cell Senescence: Hallmarks, Mechanisms, and Combating Strategies
Weng, Z., Wang, Y., Ouchi, T., Liu, H., Qiao, X., Wu, C., Zhao, Z., Li, L., & Li, B. (2022) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac004 · Cited by 291 · see citing works
Epigenetic regulation in human melanoma: past and future
Sarkar, D., Leung, E. Y., Baguley, B. C., Finlay, G. J., & Askarian-Amiri, M. (2015) · Epigenetics · doi:10.1080/15592294.2014.1003746 · Cited by 291 · see citing works
Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis
Herceg, Z., & Hainaut, P. L. (2007) · Molecular Oncology · doi:10.1016/j.molonc.2007.01.004 · Cited by 282 · see citing works
Cell cycle regulation by long non-coding RNAs
Kitagawa, M., Kitagawa, K., Kotake, Y., Niida, H., & Ohhata, T. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1423-0 · Cited by 280 · see citing works
Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage- and Histone Methylation-Dependent Pathways
Ito, T., Teo, Y. V., Evans, S. A., Neretti, N., & Sedivy, J. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.002 · Cited by 265 · see citing works
p15Ink4b is a critical tumour suppressor in the absence of p16Ink4a
Krimpenfort, P., IJpenberg, A., Song, J.-Y., van der Valk, M., Nawijn, M., Zevenhoven, J., & Berns, A. (2007) · Nature · doi:10.1038/nature06084 · Cited by 269 · see citing works
SWI/SNF Mediates Polycomb Eviction and Epigenetic Reprogramming of the INK4b-ARF-INK4a Locus
Kia, S. K., Gorski, M. M., Giannakopoulos, S., & Verrijzer, C. P. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.02019-07 · Cited by 265 · see citing works
Cellular senescence and Alzheimer disease: the egg and the chicken scenario
Saez-Atienzar, S., & Masliah, E. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-0325-z · Cited by 257 · see citing works
Long Noncoding RNA, Polycomb, and the Ghosts Haunting INK4b-ARF-INK4a Expression
Aguiló, F., Zhou, M., & Walsh, M. J. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-4379 · Cited by 255 · see citing works
Long non-coding RNAs in cancer progression
Tano, K., & Akimitsu, N. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00219 · Cited by 250 · see citing works
The Multifaceted Roles of USP7: New Therapeutic Opportunities
Nicholson, B., & Kumar, S. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9185-5 · Cited by 243 · see citing works
Roles of the Polycomb group proteins in stem cells and cancer
Richly, H., Aloia, L., & Croce, L. D. (2011) · Cell Death and Disease · doi:10.1038/cddis.2011.84 · Cited by 241 · see citing works
Transforming Growth Factor-Beta Induces Senescence in Hepatocellular Carcinoma Cells and Inhibits Tumor Growth†,‡
Şentürk, Ş., Mumcuoğlu, M., Gürsoy-Yüzügüllü, Ö., Cingoz, B., Akçalı, K. C., & Öztürk, M. (2010) · Hepatology · doi:10.1002/hep.23769 · Cited by 238 · see citing works
A Decade of GWAS Results in Lung Cancer
Bossé, Y., & Amos, C. I. (2017) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-16-0794 · Cited by 229 · see citing works
Aging and microRNA expression in human skeletal muscle: a microarray and bioinformatics analysis
Drummond, M. J., McCarthy, J. J., Sinha, M., Spratt, H. M., Volpi, E., Esser, K. A., & Rasmussen, B. B. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00148.2010 · Cited by 234 · see citing works
Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer
Zhang, Z., Zhou, C., Chang, Y., Zhang, Z., Hu, Y., Zhang, F., Lu, Y., Zheng, L., Zhang, W., Li, X., et al. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.03.022 · Cited by 234 · see citing works
Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls
Timofeeva, M. N., Hung, R. J., Rafnar, Þ., Christiani, D. C., Field, J. K., Bickeböller, H., Risch, A., McKay, J., Wang, Y., Dai, J., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds334 · Cited by 230 · see citing works
Epigenetic reprogramming of host genes in viral and microbial pathogenesis
Paschos, K., & Allday, M. J. (2010) · Trends in Microbiology · doi:10.1016/j.tim.2010.07.003 · Cited by 229 · see citing works
The cell fate: senescence or quiescence
Terzi, M. Y., Izmirli, M., & Gogebakan, B. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4065-0 · Cited by 208 · see citing works
lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer
Xu, M., Chen, X., Kang, L., Zeng, K., Liu, X., Xu, X., Pan, B., Xu, T., Sun, L., He, B., et al. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0690-5 · Cited by 214 · see citing works
Long somatic DNA-repeat expansion drives neurodegeneration in Huntington’s disease
Handsaker, R. E., Kashin, S., Reed, N. M., Tan, S., Lee, W., McDonald, T. M., Morris, K., Kamitaki, N., Mullally, C. D., Morakabati, N. R., et al. (2025) · Cell · doi:10.1016/j.cell.2024.11.038 · Cited by 214 · see citing works
Loss of Heterozygosity (LOH) Profiles—Validated Risk Predictors for Progression to Oral Cancer
Zhang, L., Poh, C. F.-Y., Williams, M., Laronde, D. M., Berean, K. W., Gardner, P. J., Jiang, H., Wu, L., Lee, J. J., & Rosin, M. P. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-12-0173 · Cited by 212 · see citing works
The pancreatic cancer genome revisited
Hayashi, A., Hong, J., & Iacobuzio-Donahue, C. A. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00463-z · Cited by 211 · see citing works
Tumour suppression by p53: the importance of apoptosis and cellular senescence
Zuckerman, V., Wolyniec, K., Sionov, R. V., Haupt, S., & Haupt, Y. (2009) · The Journal of Pathology · doi:10.1002/path.2584 · Cited by 210 · see citing works
Genistein Induces the p21WAF1/CIP1 and p16INK4a Tumor Suppressor Genes in Prostate Cancer Cells by Epigenetic Mechanisms Involving Active Chromatin Modification
Majid, S., Kikuno, N., Nelles, J. L., Noonan, E. J., Tanaka, Y., Kawamoto, K., Hirata, H., Li, L. C., Zhao, H., Okino, S. T., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2290 · Cited by 209 · see citing works
KDM2b/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia.
He, J.-Q., Nguyen, A., & Zhang, Y. (2011) · Blood · doi:10.1182/blood-2010-10-312736 · Cited by 202 · see citing works
Role of sphingolipids in senescence: implication in aging and age-related diseases
Trayssac, M., Hannun, Y. A., & Obeid, L. M. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97949 · Cited by 205 · see citing works
C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells
Zhuang, D., Mannava, S., Grachtchouk, V., Tang, W. H., Patil, S. B., Wawrzyniak, J. A., Berman, A. E., Giordano, T. J., Prochownik, E. V., Soengas, M. S., et al. (2008) · Oncogene · doi:10.1038/onc.2008.258 · Cited by 204 · see citing works
Epigenetic regulation of theINK4b-ARF-INK4alocus: In sickness and in health
Popov, N., & Gil, J. (2010) · Epigenetics · doi:10.4161/epi.5.8.12996 · Cited by 202 · see citing works
Self-citation
CDK4: A Key Player in the Cell Cycle, Development, and Cancer
Baker, S. J., & Reddy, E. P. (2012) · Genes & Cancer · doi:10.1177/1947601913478972 · Cited by 197 · see citing works
Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A‐ARF locus
Dietrich, N., Bracken, A. P., Trinh, E., Schjerling, C. K., Koseki, H., Rappsilber, J., Helin, K., & Hansen, K. H. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601632 · Cited by 187 · see citing works
Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway
Wan, G., Mathur, R., Hu, X., Liu, Y., Zhang, X., Peng, G., & Lu, X. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.02.006 · Cited by 193 · see citing works
Recent Studies of the Human Chromosome 9p21 Locus, Which Is Associated With Atherosclerosis in Human Populations
Holdt, L. M., & Teupser, D. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.232678 · Cited by 186 · see citing works
Epigenetic regulation of caloric restriction in aging
Li, Y., Daniel, M. G., & Tollefsbol, T. O. (2011) · BMC Medicine · doi:10.1186/1741-7015-9-98 · Cited by 189 · see citing works
Food Restriction Ameliorates the Development of Polycystic Kidney Disease
Warner, G. M., Hein, K. Z., Nin, V., Edwards, M., Chini, C. C. S., Hopp, K., Harris, P. C., Torres, V. E., & Chini, E. N. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015020132 · Cited by 187 · see citing works
Senescence promotes in vivo reprogramming through p16<scp>INK</scp>4a and <scp>IL</scp>‐6
Mosteiro, L., Pantoja, C., de Martino, A., & Serrano, M. (2018) · Aging Cell · doi:10.1111/acel.12711 · Cited by 182 · see citing works
Cancer and ageing: convergent and divergent mechanisms
Serrano, M., & Blasco, M. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2242 · Cited by 182 · see citing works
Cellular senescence in the aging and diseased kidney
Valentijn, F. A., Falke, L. L., Nguyen, T. Q., & Goldschmeding, R. (2018) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-017-0434-2 · Cited by 173 · see citing works
Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake
Lambert, M.-P., Paliwal, A., Vaissière, T., Chemin, I., Zoulim, F., Tommasino, M., Hainaut, P. L., Sylla, B. S., Scoazec, J., Tost, J., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.07.027 · Cited by 173 · see citing works
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D. J., Ohmura, M., Hirao, A., Saya, H., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904105 · Cited by 172 · see citing works

Epigenetic regulation of theINK4b-ARF-INK4alocus: In sickness and in health
Popov, N., & Gil, J. (2010) · Epigenetics · doi:10.4161/epi.5.8.12996 · Cited by 202 · see citing works
Self-citation
The ARF tumor suppressor: Structure, functions and status in cancer
Ozenne, P., Eymin, B., Brambilla, E. M., & Gazzéri, S. (2010) · International Journal of Cancer · doi:10.1002/ijc.25511 · Cited by 180 · see citing works
A New Mechanism of Inactivation of the INK4/ARF Locus
González, S., & Serrano, M. (2006) · Cell Cycle · doi:10.4161/cc.5.13.2901 · Cited by 57 · see citing works
INK4a/ARF: A multifunctional tumor suppressor locus
Sharpless, N. E. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.08.021 · Cited by 442 · see citing works
Tumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · see citing works

Authors: Gil, J., & Peters, G.
Affiliations: Imperial College London (GB)
Cancer Research UK (GB)
Corresponding author: Peters, Gordon
ORCID: Gil, Jesús
Venue: Nature Reviews Molecular Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2006-09-01
Volume: 7
Issue: 9
Pages: 667-677
ISSN: 1471-0072 (ISSN-L)
1471-0080
DOI: 10.1038/nrm1987
OpenAlex: W2056495027
Cited by: 843
References: 153
Citations by year: 2026: 13 · 2025: 23 · 2024: 24 · 2023: 35 · 2022: 38 · 2021: 30 · 2020: 33 · 2019: 32 · 2018: 35 · 2017: 48 · 2016: 48 · 2015: 53 · 2014: 48 · 2013: 56 · 2012: 58
FWCI: 4.03
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Molecular Cell Biology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: tumor suppressor, CDKN2B, p16INK4a, Arf proteins, cyclin-dependent kinase inhibitors, cis-regulatory elements, replicative senescence, apoptosis, stem cell self-renewal, transcriptional regulation, cancer
MeSH terms: Animals, Gene Expression Regulation, Humans, Repressor Proteins, Stem Cells, Signal Transduction, Cellular Senescence, Apoptosis, Cyclin-Dependent Kinase Inhibitor p16, ADP-Ribosylation Factors, Quantitative Trait Loci, Cyclin-Dependent Kinase Inhibitor p15, Polycomb-Group Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks