The DOI matches its Crossref record; 54 of the 56 references it cites were found in a registry or an index.
Tumor suppression by Ink4a-Arf: progress and puzzles.
Abstract
The two products of the Ink4a-Arf locus, p16(Ink4a) and p19(Arf) (p14(ARF) in humans), are potent tumor suppressors that regulate the activities of the retinoblastoma protein and the p53 transcription factor. These proteins form part of a signaling network that is disrupted in most, if not all, cancer cells. The Ink4a-Arf locus responds to stress signals, limiting cell proliferation and modulating oncogene-induced apoptosis. Recent evidence emerging from mouse tumor models distinguishes the activities of p16(Ink4a) and p19(Arf) in regulating tumor onset and identifies differences in their responsiveness to drugs.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Moreover, mutations that dampen the p53 or p16INK4a/pRB pathways confer resistance to senescence and greatly increase cancer risk [ 12 , 13 ].”
From Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor (2008) · cites this paper as [13]
In the citing paper
“In contrast, p16INK4a is poorly induced in senescent BJ fibroblasts and appears dispensable for senescence in MEFs (Beauséjour et al., submitted; Lowe and Sherr, 2003).”
From Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence (2003) · cites this paper as Lowe and Sherr, 2003
In the citing paper
“In contrast, p16INK4a is poorly induced in senescent BJ fibroblasts and appears dispensable for senescence in MEFs (Beauséjour et al., submitted; Lowe and Sherr, 2003).”
From Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence (2003) · cites this paper as Lowe and Sherr, 2003
In the citing paper
“p16 is induced by a variety of stressful stimuli, including overexpression of oncogenes such as RAS and suboptimal culture conditions (Lowe and Sherr, 2003).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Lowe and Sherr, 2003
In the citing paper
“The p16-Arf locus encodes 2 tumor suppressors, p16 and Arf.10-12”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [10]
In the citing paper
“p16 functions as a cyclin-dependent kinase (CDK) 4/6 inhibitor.10”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [10]
In the citing paper
“Therefore, activation of p53 by Arf can induce not only senescence but also apoptosis, depending on which gene downstream of p53 is induced after p53 activation.”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [10]
In the citing paper
“In contrast, the biological action of Arf relies on the p53 pathway. This is because Arf can directly bind to mouse double minute 2 homolog (MDM2) and cause the accumulation of p53 by segregating MDM2 from p53 and by inhibiting MDM2’s E3 ubiquitin protein ligase activity for p53.10,11,14”
From Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner (2014) · cites this paper as [10]
Citations
Cites
Network motifs in the transcriptional regulation network of Escherichia coli
Shen-Orr, S. S., Milo, R., Mangan, S., & Alon, U. S. (2002) · Nature Genetics · doi:10.1038/ng881 · Cited by 2,970
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580
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
Self-citationMayo, L. D., & Donner, D. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181181198 · Cited by 1,230
Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., & Klingelhutz, A. J. (1998) · Nature · doi:10.1038/23962 · Cited by 1,206
Cheng, M., Olivier, P., Diehl, J. A., Fero, M., Roussel, M. F., Roberts, J. M., & Sherr, C. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1571 · Cited by 1,142
Self-citationTelomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085
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 1,069
A Senescence Program Controlled by p53 and p16INK4a Contributes to the Outcome of Cancer Therapy
Schmitt, C. A., Fridman, J. S., Yang, M., Lee, S., Baranov, E., Hoffman, R. M., & Lowe, S. W. (2002) · Cell · doi:10.1016/s0092-8674(02)00734-1 · Cited by 1,050
Self-citationThe INK4a/ARF network in tumour suppression
Sherr, C. J. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096061 · Cited by 1,001
Self-citation
Cited by
Sorted by citations
Items 301–400 of 698
Blue, E. K., DiGiuseppe, R., Derr-Yellin, E. C., Acosta, J. C., Pay, S. L., Hanenberg, H., Schellinger, M. M., Quinney, S. K., Mund, J. A., Case, J., et al. (2013) · Pediatric Research · doi:10.1038/pr.2013.224 · Cited by 39
Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma
Huang, L. E. (2022) · Biomedicines · doi:10.3390/biomedicines10020246 · Cited by 43
“p16INK4a) promotes pRB-mediated cell-cycle checkpoints by inhibiting CDK4 (cyclin D-dependent kinase 4) that phosphorylates and inactivates pRB [9].”
BackgroundThe Role of p53 Tumor-Suppressor Protein in Apoptosis and Cancerogenesis
Maximov, G. K., & Maximov, K. G. (2008) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2008.10817532 · Cited by 46
ZRF1 controls oncogene-induced senescence through the INK4-ARF locus
Ribeiro, J. D., Morey, L., Mas, A., Gutierrez, A., Luis, N. M., Mejetta, S., Richly, H., Benitah, S. A., Keyes, W. M., & Di Croce, L. (2013) · Oncogene · doi:10.1038/onc.2012.241 · Cited by 41
Ceballos, E., Muñoz-Alonso, M. J., Berwanger, B., Acosta, J. C., Hernández, R., Krause, M., Hartmann, O., Eilers, M., & León, J. (2005) · Oncogene · doi:10.1038/sj.onc.1208652 · Cited by 43
“Thus, elevated levels of cMyc activate p53-function in cells that express ARF (reviewed in Henriksson et al., 2001; Lowe and Sherr, 2003).”
BackgroundRegulation of the INK4a/ARF Locus by Histone Deacetylase Inhibitors
Matheu, A., Klatt, P., & Serrano, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508270200 · Cited by 41
Horn, L., Richter, C. E., Einenkel, J., Tannapfel, A., Liebert, U.-G., & Leo, C. (2006) · Annals of Diagnostic Pathology · doi:10.1016/j.anndiagpath.2005.09.001 · Cited by 41
Darbro, B. W., Schneider, G. B., & Klingelhutz, A. J. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23844.x · Cited by 42
“…stimulus for p16 induction under certain culture conditions has not been fully elucidated; however, it has been proposed that cellular stress is responsible for this change in gene expression (Sherr and DePinho, 2000;Shay and Wright, 2001;Lowe and Sherr, 2003;BenPorath and Weinberg, 2004).”
BackgroundA Novel Nuclear Interactor of ARF and MDM2 (NIAM) That Maintains Chromosomal Stability
Tompkins, V. S., Hagen, J., Frazier, A. A., Lushnikova, T., Fitzgerald, M. P., Tommaso, A. D., Ladevèze, V., Domann, F. E., Eischen, C. M., & Quelle, D. E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609612200 · Cited by 40
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 42
“Human cells seem to require disruption of both INK4A-pRb and ARF-p53 pathways to bypass replicative senescence (Drayton et al., 2003; Lowe and Sherr, 2003).”
BackgroundExploiting the p53 Pathway for the Diagnosis and Therapy of Human CancerPreprint
Lane, D. P. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.049 · Cited by 40
A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia
Chen, Y., Sullivan, C., Peng, C., Shan, Y., Hu, Y., Li, D., & Li, S. (2011) · Blood · doi:10.1182/blood-2010-11-316760 · Cited by 40
The zinc finger transcription factor ZFHX1A is linked to cell proliferation by Rb–E2F1
Liu, Y., Costantino, M. E., Montoya-Durango, D. E., Higashi, Y., Darling, D. S., & Dean, D. C. (2007) · Biochemical Journal · doi:10.1042/bj20070344 · Cited by 39
Tran, M., Jinesh, G. G., McConkey, D. J., & Kamat, A. M. (2010) · Current Stem Cell Research & Therapy · doi:10.2174/157488810793351640 · Cited by 39
“Inhibition of tumor suppressors such as p16 INK4a , p19 ARF (p14 ARF in human), and p53 by Bmi1 is involved not only in tumor proliferation but also in stem cell self-renewal [48-50].”
BackgroundGene regulatory network underlying the immortalization of epithelial cells
Méndez-López, L. F., Dávila-Velderrain, J., Domínguez‐Hüttinger, E., Enríquez-Olguín, C., Martínez‐García, J. C., & Alvarez-Buylla, E. R. (2017) · BMC Systems Biology · doi:10.1186/s12918-017-0393-5 · Cited by 41
“…inflammation by increasing the expression of NF– κ B [43]. p16 promotes its own activity forming a positive feedback loop [44], stabilizes p53 via the inactivation of its inhibitor MDM2 [45], and inhibits the cell cycle progression by the induction of Rb [46] and the inhibition of cyclin [23, 28].”
Full-length hdmX transcripts decrease following genotoxic stress
Markey, M., & Berberich, S. J. (2008) · Oncogene · doi:10.1038/onc.2008.266 · Cited by 38
“The tumor suppressor p14ARF is able to stabilize p53 by promoting the autoubiquitination and degradation of Hdm2 (Honda and Yasuda, 1999; Lowe and Sherr, 2003), consistent with its inactivation being observed in human tumors.”
Kuroda, K., Fukuda, T., Hiroshi Yoneyama, C., Katayama, M., Isogai, H., Okumura, K., & Isogai, E. (2012) · Oncology Reports · doi:10.3892/or.2012.1876 · Cited by 38
HMGA2 and the p19Arf‐TP53‐CDKN1A axis: A delicate balance in the growth of uterine leiomyomas
Markowski, D. N., von Ahsen, I., Nezhad, M. H., Wosniok, W., Helmke, B. M., & Bullerdiek, J. (2010) · Genes Chromosomes and Cancer · doi:10.1002/gcc.20777 · Cited by 38
Hallmarks for senescence in carcinogenesis: novel signaling players
Caino, M. C., Meshki, J., & Kazanietz, M. G. (2009) · APOPTOSIS · doi:10.1007/s10495-009-0316-z · Cited by 40
Mikula, M., Fuchs, E., Huber, H., Beug, H., Schulte‐Hermann, R., & Mikulits, W. (2004) · Hepatology · doi:10.1002/hep.20084 · Cited by 38
Natoli, C., Ramazzotti, V., Nappi, O., Giacomini, P., PALMERI, S., Salvatore, M., Landriscina, M., Zilli, M., Natali, P. G., Tinari, N., et al. (2011) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2011.02.002 · Cited by 37
“The higher incidence of p53 mutation detected by IHC as compared to that observed by mutational analysis may have different explanations: i) the occurrence of mutations outside the exon 5–9 region [43]; ii) monoclonal antibodies used in IHC can detect both wild and mutated protein [44]; iii) presence of alterations in…”
BackgroundValente, L. J., Grabow, S., Vandenberg, C. J., Strasser, A., & Janic, A. (2015) · Oncogene · doi:10.1038/onc.2015.457 · Cited by 37
Leg Amputation Accelerates Senescence of Rat Lumbar Intervertebral Discs
Xing, Q.-J., Liang, Q.-Q., Bian, Q., Ding, D.-F., Cui, X.-Q., Shi, Q., & Wang, Y.-J. (2010) · Spine · doi:10.1097/brs.0b013e3181e7d087 · Cited by 37
“p19ARF is induced in cultured primary cells and can cause these cells to senesce.(22) The replicative lifespan of primary cells can be extended and senescence can be prevented by reducing p19ARF and p16INK4a expression.”
BackgroundExpression of p14, MDM2, and MDM4 in human retinoblastoma
Guo, Y., Pajovic, S., & Gallie, B. L. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.07.055 · Cited by 36
“MDM2 is overexpressed in 5–10% of human tumors, potentially resulting in disruption the p14ARFMDM2-p53 pathway [2,11].”
BackgroundLoss of p73 promotes dissemination of Myc-induced B cell lymphomas in mice
Nemajerová, A., Petrenko, O., Trümper, L. H. P., Palacios, G. F., & Moll, U. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40331 · Cited by 37
Menzel, O., Migliaccio, M., Goldstein, D. R., Dahoun, S. P., Delorenzi, M., & Rufer, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3657 · Cited by 38
Miyazaki, M., Miyazaki, K., Chen, S., Chandra, V. K., Wagatsuma, K., Agata, Y., Rodewald, H.-R., Saito, R., Chang, A. N., Varki, N. M., et al. (2015) · Genes & Development · doi:10.1101/gad.255331.114 · Cited by 37
“Finally, we found that c-Myc and p19Arf levels were elevated in Id -depleted CD4SP thymocytes. p19Arf is a well-known tumor suppressor that is regulated by c-Myc (Lowe and Sherr 2003).”
Sivakolundu, S. G., Nourse, A., Moshiach, S., Bothner, B. B., Ashley, C., Satumba, J., Lahti, J. M., & Kriwacki, R. W. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.09.019 · Cited by 36
“Oncogene activation and inappropriate mitogenic signaling activate the expression of Arf, which binds to Hdm2 and relieves inhibition of p53, ultimately leading to p53-dependent and p53-independent cell cycle arrest or apoptosis.(38,39) While the importance of Arf and Hdm2 in tumor biology is well established, little…”
BackgroundTripaldi, R., Stuppia, L., & Alberti, S. (2013) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2013.02.002 · Cited by 36
“This, in turn, leads to higher p53 levels [124], thus providing a feedback regulatory loop for c-Myc expression levels.”
BackgroundTaking Human Cancer Genes to the Fish: A Transgenic Model of Melanoma in Zebrafish
Patton, E. E., & Zon, L. I. (2005) · Zebrafish · doi:10.1089/zeb.2005.1.363 · Cited by 36
Turning ON Caspases with Genetics and Small Molecules
Morgan, C. W., Julien, O., Unger, E. K., Shah, N. M., & Wells, J. A. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-417158-9.00008-x · Cited by 37
“This apoptotic suppression is usually achieved by making lesions in signaling pathways upstream of the caspases, such as p53 (Lowe & Sherr, 2003).”
An Integrated Computational/Experimental Model of Lymphoma Growth
Frieboes, H. B., Smith, B. R., Chuang, Y.-L., Ito, K., Roettgers, A. M., Gambhir, S. S., & Vittorio Cristini, C. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003008 · Cited by 35
“We chose this in vivo model because it captures genetic and pathological features of the human disease and, given the appropriate genetic mutation, drugresistant and drug-sensitive tumors can be directly compared [39,40].”
BackgroundChen, M.-H., Qi, C. X. Y., Saha, M. N., & Chang, H. (2012) · American Journal of Clinical Pathology · doi:10.1309/ajcphc85dgaxzdbe · Cited by 35
Hagen, J., Muniz, V. P., Falls, K. C., Reed, S. M., Taghiyev, A. F., Quelle, F. W., Gourronc, F. A., Klingelhutz, A. J., Major, H. J., Askeland, R. W., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3742 · Cited by 35
“Whereas p16INK4a enforces retinoblastoma (Rb1) antiproliferative activity in G1 phase, ARF promotes p53-mediated cell-cycle arrest and apoptosis (15).”
BackgroundChurchman, M. L., Roig, I., Jasin, M., Keeney, S., & Sherr, C. J. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002157 · Cited by 35
“cyclin D-dependent kinases (Cdk4 and Cdk6), as well as a third protein (p19) that antagonizes the Mdm2 ubiquitin E3 ligase to activate p53 [1].”
BackgroundSelf-citationTemporal and epigenetic regulation of neurodevelopmental plasticity
Allen, N. D. (2007) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.2010 · Cited by 35
Different cooperating effect of p21 or p27 deficiency in combination with INK4a/ARF deletion in mice
Martín‐Caballero, J., Flores, J. M., Garcı́a, P., Collado, M., & Serrano, M. (2004) · Oncogene · doi:10.1038/sj.onc.1207863 · Cited by 35
“INK4a produces p16, a Dtype cyclin kinase inhibitor, while ARF promotes p53 stability and function (Lowe and Sherr, 2003).”
BackgroundNovel Nucleolar Pathway Connecting Intracellular Energy Status with p53 Activation
Kumazawa, T., Nishimura, K., Kuroda, T., Ono, W., Yamaguchi, C., Katagiri, N., Tsuchiya, M., Masumoto, H., Nakajima, Y., Murayama, A., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.209916 · Cited by 34
p14ARF, a Prognostic Predictor in HPV-Negative Vulvar Carcinoma
Knopp, S., Nesland, J. M., Trope, C. G., & Holm, R. (2006) · American Journal of Clinical Pathology · doi:10.1309/e9e8y9wg5qe3lk29 · Cited by 34
“8) Yes 25/46 28 18 (39) 22 24 (52) 39 7 (15) NA 0/3 3 0 (0) 3 0 (0)”
PPAR trilogy from metabolism to cancer
Nahle, Z. A. (2004) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/01.mco.0000134360.30911.bb · Cited by 34
Expression of Dmp1 in specific differentiated, nonproliferating cells and its regulation by E2Fs
Mallakin, A., Taneja, P., Matise, L. A., Willingham, M. C., & Inoue, K. (2006) · Oncogene · doi:10.1038/sj.onc.1209750 · Cited by 34
“…state (Sherr and Roberts, 1999). p19Arf binds to the p53 negative regulator, Mdm2, thereby stabilizing and activating p53 (Sherr, 2001; Lowe and Sherr, 2003). p19Arf is induced by potentially harmful growth-promoting signals resulting from overexpression of a variety of oncoproteins,…”
BackgroundAberrant histone modification in endometriosis
Nasu, K. (2014) · Frontiers in bioscience · doi:10.2741/4276 · Cited by 33
“p16 is a CDK inhibitor that controls cellcycle progression during the G1 phase by inhibiting the ability of cyclin D–CDK4 and cyclin D–CDK6 complexes to phosphorylate retinoblastoma 1 (RB1) (61, 62).”
BackgroundRepression of Dmp1 and Arf transcription by anthracyclins: critical roles of the NF-κB subunit p65
Taneja, P., Mallakin, A., Matise, L. A., Frazier, D. P., Choudhary, M., & Inoue, K. (2007) · Oncogene · doi:10.1038/sj.onc.1210568 · Cited by 34
Optimal time for passaging neurospheres based on primary neural stem cell cultures
Xiong, F., Gao, H., Yan, Z., Chen, X., Lin, W., Shen, J., Yan, Y., Wang, X., Liu, M., & Gao, Y. (2011) · Cytotechnology · doi:10.1007/s10616-011-9379-0 · Cited by 34
“In addition, p16Ink4a inhibits NSC self-renewal in culture (Molofsky et al. 2003).”
Genetic variants on chromosome 9p21 and ischemic stroke in Chinese
Hu, W.-L., Li, S., Liu, D., Wang, Y., Niu, S., Yang, X., Zhang, Q., Yu, S., Li, J., & Wang, X. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.04.001 · Cited by 34
Hzf, a p53-Responsive Gene, Regulates Maintenance of the G2 Phase Checkpoint Induced by DNA Damage
Sugimoto, M., Gromley, A., & Sherr, C. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.2.502-512.2006 · Cited by 35
“Apart from the DNA damage response, aberrant growth-promoting signals emanating from oncogenes can also activate p53 by inducing the tumor suppressor, p19 (p14 in humans), which binds to Mdm2 and antagonizes its E3 ubiquitin ligase activity (40).”
BackgroundSelf-citationDNA tumor viruses — the spies who lyse us
O’Shea, C. C. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.12.010 · Cited by 34
Vukićević, V., Jauch, A. S., Dinger, T. C., Gebauer, L., Hornich, V., Bornstein, S. R., Ehrhart‐Bornstein, M., & Müller, A. M. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.01.001 · Cited by 33
Areca-treated Fibroblasts Enhance Tumorigenesis of Oral Epithelial Cells
Lu, H., Liu, C., Liu, T.-Y., Kao, S., Lin, S., & Chang, K. (2008) · Journal of Dental Research · doi:10.1177/154405910808701111 · Cited by 34
S6 Kinase- and β-TrCP2-Dependent Degradation of p19Arf Is Required for Cell Proliferation
Nakagawa, T., Araki, T., Nakagawa, M., Hirao, A., Unno, M., & Nakayama, K. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.00343-15 · Cited by 33
“2C), suggesting that p19 accumulation did not result from transcriptional regulation; and (iii) induction of p53 and p21 in the mutant MEFs was likely the result of p19 accumulation (28), a notion supported by the observation that the amount of p21 mRNA was increased in -TrCP2 / MEFs (Fig.”
ResultZhao, Y., Zhang, Y., Yang, Z., Li, A., & Dong, J. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.03.148 · Cited by 31
Advances in the molecular biology of malignant mesothelioma.
Toyooka, S., Kishimoto, T., & Date, H. (2008) · PubMed · doi:10.18926/amo/30990 · Cited by 33
“In addition, the loss of p14 protein results in the activation of mdm(2) protein, a p53 ubiquitin ligase, and this activation is thought to be linked to the destabilization of p53 protein, thus causing alterations in cell cycle control [22] (Fig.”
BackgroundStable Form of JAB1 Enhances Proliferation and Maintenance of Hematopoietic Progenitors
Mori, M., Yoneda‐Kato, N., Yoshida, A., & Kato, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804539200 · Cited by 33
Hasan, M., Yaguchi, T., Harada, J., Hirano, T., Wadhwa, R., & Kaul, S. C. (2008) · International Journal of Oncology · doi:10.3892/ijo.32.3.663 · Cited by 33
Kreisel, F. H. C., Kulkarni, S., Kerns, R. T., Hassan, A., Deshmukh, H., Nagarajan, R., Frater, J. L., & Cashen, A. F. (2011) · Cancer Genetics · doi:10.1016/j.cancergen.2010.12.010 · Cited by 32
Montalbano, J., Jin, W., Sheikh, M. S., & Huang, Y. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704760200 · Cited by 32
Physical and Functional Interaction between Ribosomal Protein L11 and the Tumor Suppressor ARF
Dai, M., Challagundla, K. B., Sun, X., Palam, L. R., Zeng, S. X., Wek, R. C., & Lu, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.311902 · Cited by 31
“These ARF functions consequently activate p53 and induce cell cycle arrest, apoptosis, or senescence (13, 24).”
BackgroundJin, X., Eroglu, B., Cho, W., Yamaguchi, Y., Moskophidis, D., & Mivechi, N. F. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0530 · Cited by 34
“This locus is deleted in many human tumors (26).”
BackgroundFikaris, A. J., Lewis, A. E., Abulaiti, A., Tsygankova, O. M., & Meinkoth, J. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606737200 · Cited by 33
Pluripotency transcription factors in lung cancer—a review
Sławek-Szmyt, S., Szmyt, K., Fularz, M., Dziudzia, J., Boruczkowski, M., Sikora, J., & Kaczmarek, M. (2015) · Tumor Biology · doi:10.1007/s13277-015-4407-x · Cited by 31
Liu, Y., Sànchez‐Tilló, E., Lu, X., Huang, L. F., Clem, B. F., Telang, S., Jenson, A. B., Cuatrecasas, M., Chesney, J. A., Postigo, A. A., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.434951 · Cited by 31
“Because p21 is a target of p53 (33), wewonderedwhether p53 might be required for senescence of MEFs when ZEB1 is knocked down.”
BackgroundModeling aging and cancer in the telomerase knockout mouse
Chang, S. S. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.020 · Cited by 32
Stochastic and Deterministic Models of Cellular p53 Regulation
Leenders, G. B., & Tuszyński, J. A. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00064 · Cited by 28
“ARF is negatively regulated by p53 in a complex manner, thus forming a feedback loop (Stott et al., 1998; Lowe and Sherr, 2003).”
BackgroundXu, N., Li, Y.-L., Zhou, X., Cao, R., Li, H., Lu, Q., Li, L., Lu, Z., Huang, J., Sun, J., et al. (2015) · Journal of Cancer · doi:10.7150/jca.11959 · Cited by 29
“[2-4].”
Pallante, P., Malapelle, U., Berlingieri, M. T., Bellevicine, C., Sepe, R., Federico, A., Rocco, D., Galgani, M., Chiariotti, L., Sánchez‐Céspedes, M., et al. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2012.09.033 · Cited by 30
Modulation of the ARF-p53 Pathway by the Small DNA Tumor Viruses
O’Shea, C. C., & Fried, M. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1555 · Cited by 29
Ito, K., Maruyama, Z., Sakai, A., Izumi, S., Moriishi, T., Yoshida, C. A., Miyazaki, T., Komori, H., Takada, K., Kawaguchi, H., et al. (2013) · Oncogene · doi:10.1038/onc.2013.130 · Cited by 30
Spandidos, D. A. (1994) · Oncology Reports · doi:10.3892/or_00000070 · Cited by 31
Bypassing melanocyte senescence by β-catenin: A novel way to promote melanoma
Larue, L., Luciani, F., Kumasaka, M. Y., Champeval, D., Demirkan, N. Ç., Bonaventure, J., & Delmas, V. (2009) · Pathologie Biologie · doi:10.1016/j.patbio.2008.11.003 · Cited by 32
E2F3—A Novel Repressor of the ARF/p53 Pathway
Ginsberg, D. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.05.012 · Cited by 30
Martel, V., Filhol, O., Colas, P., & Cochet, C. (2006) · Oncogene · doi:10.1038/sj.onc.1209722 · Cited by 30
“Activation of p53 usually initiates the apoptotic pathway in these cells (Lowe and Sherr, 2003).”
BackgroundA functional link between the tumour suppressors ARF and p33ING1
Gonzalez, L. C., Freije, J. M. P., Cal, S., López-Otı́n, C., Serrano, M., & Palmero, I. (2006) · Oncogene · doi:10.1038/sj.onc.1209526 · Cited by 30
“ARF exerts its tumor suppressor action through the activation of p53, in response to a variety of stress signals (Sherr, 2001; Lowe and Sherr, 2003).”
BackgroundPrecocious G1/S transitions and genomic instability: the origin connection
Sidorova, J. M., & Breeden, L. L. (2003) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2003.08.006 · Cited by 30
Decreased Mdm2 expression inhibits tumor development induced by loss of ARF
Wang, P., Greiner, T. C., Lushnikova, T., & Eischen, C. M. (2006) · Oncogene · doi:10.1038/sj.onc.1209411 · Cited by 29
“ARF expression is lost in tumors by biallelic deletion of the entire ARF/Ink4a locus or by methylation of a CpG island in the ARF promoter (reviewed in Lowe and Sherr, 2003).”
BackgroundPeng, L. H., Mayhew, C. N., Schnekenburger, M., Knudsen, E. S., & Puga, A. (2008) · Toxicology · doi:10.1016/j.tox.2008.01.002 · Cited by 30
“…rather than repression of p18 (Cdkn2c) and argues against a pure tumor suppressor role for this gene (Joshi et al., 2007; Lindberg, Akerstrom, and Westin, 2007; Pei et al., 2007), whereas p19/ARF (Cdkn2d) is almost exclusively repressed in tumors (Lowe and Sherr, 2003; Canepa et al., 2007).”
BackgroundReactivating the ARF-p53 axis in AML cells by targeting ULF
Chen, D., Yoon, J., & Gu, W. J. (2010) · Cell Cycle · doi:10.4161/cc.9.15.12355 · Cited by 33
“the GSt-NPM (187-294) (lane 5), GSt-NPM (118-186) (lane 4), GSt-NPM (1-117) (lane 3) or GSt alone (lane 2) were used in a GSt pull-down assay with in vitro translated 35S-labeled ULF.”
BackgroundMethodGlobule Leukocytes and Other Mast Cells in the Mouse Intestine
Vogel, P., Janke, L. J., Gravano, D. M., Lu, M., Sawant, D. V., Bush, D. A., Shuyu, E., Vignali, D. A. A., Pillai, A., & Rehg, J. E. (2017) · Veterinary Pathology · doi:10.1177/0300985817705174 · Cited by 31
“Increased tumor development is associated with a loss of function of INK4a, ARF, Rb, or p53.(126) The equivalent protein in mice is p19ARF, and mice lacking p19ARF develop a wide range of tumors at relatively young ages.”
Bowman, P., Galea, C. A., Lacy, E. R., & Kriwacki, R. W. (2006) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2005.12.016 · Cited by 29
miR‐20a and miR‐290, multi‐faceted players with a role in tumourigenesis and senescence
Rizzo, M., Mariani, L., Pitto, L., Rainaldi, G., & Simili, M. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01173.x · Cited by 28
“This locus encodes, by alternate reading frames, two different proteins p19ARF (mouse) or p14ARF (human) and p16INK4a [12], which activate, respectively, p53 and RB [13].”
BackgroundJat, P., Perkins, N. D., & Mowla, S. N. (2013) · OncoTargets and Therapy · doi:10.2147/ott.s36160 · Cited by 33
“This prevents the phosphorylation and deactivation of the pRB family of pocket proteins permitting hypophosphorylated pRB to complex with the E2F family of heterodimeric TFs.47 In turn, pRB recruits histone deacetylases and remodeling factors to E2F responsive promoters, thereby inhibiting E2F-dependent S-phase gene e…”
BackgroundHesse, R. G., Kouklis, G. K., Ahituv, N., & Pomerantz, J. H. (2015) · eLife · doi:10.7554/elife.07702 · Cited by 28
“DOI: 10.7554/eLife.07702.001”
BackgroundInfluentialNaemura, M., Tsunoda, T., Inoue, Y., Okamoto, H., Shirasawa, S., & Kotake, Y. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2618-5 · Cited by 28
“These genes positively regulate the pRB and p53 pathways, which play pivotal roles in tumor suppression [9].”
BackgroundModeling the response of a tumor-suppressive network to mitogenic and oncogenic signals
Tian, X., Huang, B. Y., Zhang, X., Lu, M., Liu, F., Onuchic, J. N., & Wang, W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702412114 · Cited by 28
“This result agrees with the experimental observations that ARF becomes active only when the levels of its inducers exceed aberrantly high thresholds (14, 34, 35).”
ResultMoulana, I., Priyani, A. A. H., de Silva, M. V. C., & Dassanayake, R. S. (2017) · Hormones and Cancer · doi:10.1007/s12672-017-0315-4 · Cited by 29
Rotolo, S., Diotti, R., Gordon, R. E., Qiao, R., Yao, Z., Phelps, R. G., & Dong, J. (2005) · International Journal of Cancer · doi:10.1002/ijc.20865 · Cited by 28
“ulator p16, which binds to and inhibits CDK4/6 and promotes cell cycle arrest via the RB tumor-suppressor pathway.(13,14) Consistent with a tumor-suppressor role of INK4A in melanomas, a”
Backgroundp14ARF, p15INK4band p16INK4aMethylation Status in Chronic Myelogenous Leukemia
Kusy, S., Larsen, C., & Roche, J. (2004) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428190410001714025 · Cited by 27
“FIGURE 2 Description of the functions of p14 and p16 adapted from [4].”
BackgroundFrom tumor prevention to therapy: Empowering p53 to fight back
Frezza, C., & Martins, C. P. (2012) · Drug Resistance Updates · doi:10.1016/j.drup.2012.10.001 · Cited by 27
Zheng, Y., Zhao, Y. D., Gibbons, M. A., Abramova, T. V., Chu, P. Y., Ash, J. D., Cunningham, J. M., & Skapek, S. X. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.128959 · Cited by 27
Hematological malignancies: disease pathophysiology of leukemic stem cells.
Ramdass, B., Chowdhary, A. S., & Koka, P. S. (2013) · PubMed · Cited by 27
Prognostic and Predictive Value of Cell Cycle Deregulation in Non-Small-Cell Lung Cancer
Sterlacci, W., Fiegl, M., & Tzankov, A. (2012) · Pathobiology · doi:10.1159/000336462 · Cited by 27
The tumor suppressor p16Ink4a regulates T lymphocyte survival
Bianchi, T., Rufer, N., MacDonald, H. R., & Migliaccio, M. (2006) · Oncogene · doi:10.1038/sj.onc.1209437 · Cited by 27
“…suggest that p16 is a checkpoint protein that does not participate in the control of normal cell proliferation, and whose expression is triggered only in some particular circumstances such as cell stress, cell senescence or the activation of certain oncogenes (Roussel, 1999; Lowe and Sherr, 2003).”
BackgroundMonoclonal Antibodies to the Mouse p19 Arf Tumor Suppressor Protein
Bertwistle, D., Zindy, F., Sherr, C. J., & Roussel, M. F. (2004) · Hybridoma and Hybridomics · doi:10.1089/hyb.2004.23.293 · Cited by 27
“On the other hand, because abnormally high and sustained thresholds of mitogenic signals induce Arf , (38) its expression may mark pre-malignant lesions that may otherwise be hard to identify in situ .”
Self-citationSimultaneous inhibition of MEK and CDK4 leads to potent apoptosis in human melanoma cells
Li, J., Xu, M., Yang, Z., Li, A., & Dong, J. (2010) · Cancer Investigation · doi:10.1080/07357900903286966 · Cited by 26
“Both ERK signaling and CDK4/6 kinase have been shown to regulate RB protein and cell cycle progression (14, 15).”
BackgroundUlanet, D., & Hanahan, D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012454 · Cited by 26
“ligase and stabilization of p53 [5].”
ARF antagonizes the ability of Miz-1 to inhibit p53-mediated transactivation
Miao, L., Song, Z., Jin, L., Zhu, Y., Wen, L., & Wu, M. (2009) · Oncogene · doi:10.1038/onc.2009.372 · Cited by 26
Chang, H., Jiang, A., & Qi, C. X. Y. (2009) · American Journal of Clinical Pathology · doi:10.1309/ajcpepx1c7hhfelk · Cited by 26
“1775 Median (range) platelet count (× 109/L) 174 (11-396) 171 (11-396) 181 (101-275) .”
Divide or Commit – Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis
Urbach, A., & Witte, O. W. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00055 · Cited by 26
Role of DMP1 and its future in lung cancer diagnostics
Sugiyama, T., Frazier, D. P., Taneja, P., Morgan, R. L., Willingham, M. C., & Inoue, K. (2008) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.8.4.435 · Cited by 26
mTOR-Independent Translational Control of the Extrinsic Cell Death Pathway by RalA
Panner, A., Nakamura, J. L., Parsa, A. T., Rodriguez‐Viciana, P., Berger, M. S., Stokoe, D., & Pieper, R. O. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00126-06 · Cited by 27
Ravid, O., Shoshani, O., Sela, M., Weinstock, A., Sadan, T. W., Gur, E., Zipori, D., & Shani, N. (2014) · Stem Cell Research & Therapy · doi:10.1186/scrt529 · Cited by 25
“BM MSCs The p19 and p16 proteins are important tumor suppressors [24].”
BackgroundResult
Metadata
- Authors
- Lowe, S. W., & Sherr, C. J.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Lowe, Scott W
- Sherr, Charles J
- Venue
- Current Opinion in Genetics & Development
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 13
- Issue
- 1
- Pages
- 77-83
- ISSN
- 0959-437X (ISSN-L)
- OpenAlex
- W1984948591
- Cited by
- 699
- References
- 56
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 20 · 2022: 10 · 2021: 5 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 17 · 2016: 17 · 2015: 29 · 2014: 30 · 2013: 48 · 2012: 34
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Genetics & Development (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- 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 › PI3K/AKT/mTOR signaling in cancer
- Keywords
- INK4a/ARF locus, p16INK4a, p19ARF, tumor suppression, retinoblastoma protein, p53, stress signaling, cell proliferation, tumor onset, mouse tumor model, drug response
- MeSH terms
- Animals, Humans, Lymphoma, Neoplasms, Tumor Suppressor Protein p53, Retinoblastoma Protein, Cyclin-Dependent Kinase Inhibitor p16, ADP-Ribosylation Factors, Feedback, Physiological, Mice, Rats
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
