The DOI matches its Crossref record; 150 of the 153 references it cites were found in a registry or an index.
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
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.
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In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“In agreement with p16's role as a guardian of senescence, mutations, silencing or loss of CDKN2A, the gene encoding p16, facilitate senescence bypass and it is frequently associated with carcinogenesis (reviewed in.51,52”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [51]
Citations
Cites
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
RetractedA 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
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 5,218 · cited 1×
“Importantly, oncogenic signalling can elicit a senescence-like arrest that is attributable to effects on the INK4b–ARF–INK4a locus, whether direct or indirec”
BackgroundProliferation, cell cycle and apoptosis in cancer
Evan, G. I., & Vousden, K. H. (2001) · Nature · doi:10.1038/35077213 · Cited by 3,417
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
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
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 2,568
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 2,379
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 2,296
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
Flagged first, then by citations
3 of the 153 references couldn’t be matched to a known paper.
Cited by
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
Molecular Mechanisms of Long Noncoding RNAs
Wang, K., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.018 · Cited by 4,462
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
“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
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
Metadata
- 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
- Published
- 2006-09-01
- Volume
- 7
- Issue
- 9
- Pages
- 667-677
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- 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
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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
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