The DOI matches its Crossref record; 90 of the 90 references it cites were found in a registry or an index.
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing
Open accessAbstract
The cyclin-dependent kinase inhibitor p21(WAF1/CIP1) (p21) is a cell-cycle checkpoint effector and inducer of senescence, regulated by p53. Yet, evidence suggests that p21 could also be oncogenic, through a mechanism that has so far remained obscure. We report that a subset of atypical cancerous cells strongly expressing p21 showed proliferation features. This occurred predominantly in p53-mutant human cancers, suggesting p53-independent upregulation of p21 selectively in more aggressive tumour cells. Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. Mechanistically, sustained p21 accumulation inhibited mainly the CRL4-CDT2 ubiquitin ligase, leading to deregulated origin licensing and replication stress. Collectively, our data reveal the tumour-promoting ability of p21 through deregulation of DNA replication licensing machinery-an unorthodox role to be considered in cancer treatment, since p21 responds to various stimuli including some chemotherapy drugs.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Similar characteristics were seen in CIP1 -overexpressing TP53 -null cultured cancer cells, which entered a transient senescent state but quickly escaped with enhanced cancer stem cell properties and an aggressive phenotype 190 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [190]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although the senescence cell-cycle arrest is generally irreversible, cell-cycle re-entry can occur under certain circumstances, particularly in tumor cells (Galanos et al., 2016; Milanovic et al., 2018; Patel et al., 2016; Saleh et al., 2019) (Figure 2).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Galanos et al., 2016
In the citing paper
“Because p21 overexpression caused the downregulation of RAD51 [71], DSBs were processed by error-prone pathways, including RAD52-dependent break-induced replication (BIR) and single-strand annealing (SSA) [75], and possibly nonhomologous end-joining [71].”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“Because both rereplication and error-prone DSB repair fuel genomic instability, these observations indicate a pro-oncogenic role of p21, at least in p53-negative cancer [71,75].”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“Moreover, replication-fork progression was asymmetric and slow, and DSBs accumulated in a manner that depended on CDT1 and CDC6 overexpression.”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“p21-overexpressing cells acquired the capacity to rereplicate.”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“The dependency on PCNA was confirmed using a p21 mutant with a disrupted PIP box (Q144A, M147A, and F150A), which did not cause CDT1 and CDC6 upregulation [71].”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“By exploring markers of active replication (KI67) and p21 levels in human tumors, unexpected colocalization of p21 and ki67 was observed in approximately 5% to 7% of cells within p53-deficient tumors [71].”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [71]
In the citing paper
“Although the cell cycle arrest in cellular senescence is believed to be irreversible, studies have recently shown that senescent cells can under certain circumstances re-enter the cell cycle such as in tumor cells (Galanos et al., 2016; Patel et al., 2016; Milanovic et al., 2018; Saleh et al., 2019) or be reprogrammed into induced pluripotent stem cells (Banito and Gil, 2010; Lapasset et al., 2011”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Galanos et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
RetractedThe Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414
Genomic instability — an evolving hallmark of cancer
Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2858 · Cited by 2,397
Self-citationThe causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262
Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
Bartkova, J., Rezaei, N., Liontos, M., Karakaidos, P., Kletsas, D., Issaeva, N., Vassiliou, L.-V. F., Kolettas, E., Niforou, K., Zoumpourlis, V. C., et al. (2006) · Nature · doi:10.1038/nature05268 · Cited by 1,986
Self-citationAn Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851
Self-citationBreakDancer: an algorithm for high-resolution mapping of genomic structural variation
Chen, K., Wallis, J. W., McLellan, M. D., Larson, D. E., Kalicki, J. M., Pohl, C. S., McGrath, S. D., Wendl, M. C., Zhang, Q., Locke, D. P., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1363 · Cited by 1,489
Reversal of human cellular senescence: roles of the p53 and p16 pathways
Beauséjour, C. M., Krtolica, A., Galimi, F., Narita, M., Lowe, S. W., Yaswen, P., & Campisi, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg417 · Cited by 1,457
Ackerman, L. V., & Rosaí, J. (1974) · Medical Entomology and Zoology · Cited by 1,042
Rivlin, N., Brosh, R., Oren, M., & Rotter, V. (2011) · Genes & Cancer · doi:10.1177/1947601911408889 · Cited by 1,033
Using the Student's t-test with extremely small sample sizes
de Winter, J. C. F. (2013) · University of Massachusetts Amherst · doi:10.7275/e4r6-dj05 · Cited by 992
A faster circular binary segmentation algorithm for the analysis of array CGH data
Venkatraman, E. S., & Olshen, A. B. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btl646 · Cited by 963
Pines, J., & Hunter, T. R. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.115.1.1 · Cited by 867
Agarwal, M. L., Agarwal, A., Taylor, W. R., & Stark, G. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.18.8493 · Cited by 858
Nucleotide deficiency promotes genomic instability in early stages of cancer development
Bester, A. C., Roniger, M., Oren, Y. S., Im, M. M., Sarni, D., Chaoat, M., Bensimon, A., Zamir, G., Shewach, D. S., & Kerem, B. (2011) · Cell · doi:10.1016/j.cell.2011.03.044 · Cited by 858
Hastings, P. J., Ira, G., & Lupski, J. R. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000327 · Cited by 818
Niculescu, A. B., Chen, X., Smeets, M. F. M. A., Hengst, L., Prives, C. L., & Reed, S. I. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.1.629 · Cited by 725
Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator
Perkins, N. D., Felzien, L. K., Betts, J. C., Leung, K., Beach, D., & Nabel, G. J. (1997) · Science · doi:10.1126/science.275.5299.523 · Cited by 720
Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells
Zellweger, R., Dalcher, D., Mutreja, K., Berti, M., Schmid, J. A., Herrador, R., Vindigni, A., & Lopes, M. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201406099 · Cited by 691
Self-citationPreventing re-replication of chromosomal DNA
Blow, J. J., & Dutta, A. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1663 · Cited by 664
Self-citationReplication fork reversal in eukaryotes: from dead end to dynamic response
Neelsen, K. J., & Lopes, M. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3935 · Cited by 523
Self-citationHallmarks of senescence in carcinogenesis and cancer therapy
Shay, J. W., & Roninson, I. B. (2004) · Oncogene · doi:10.1038/sj.onc.1207518 · Cited by 502
Self-citationCooks, T., Pateras, I. S., Tarcic, O., Solomon, H., Schetter, A. J., Wilder, S., Lozano, G., Pikarsky, E., Forshew, T., Rozenfeld, N., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.03.022 · Cited by 478
Self-citationIdentification of Early Replicating Fragile Sites that Contribute to Genome Instability
Barlow, J. H., Faryabi, R. B., Callén, E., Wong, N., Malhowski, A. J., Chen, H. T., Gutierrez-Cruz, G., Sun, H., McKinnon, P. J., Wright, G. W., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.006 · Cited by 464
Roninson, I. B. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00847-3 · Cited by 443
Self-citationNuclear Dynamics of PCNA in DNA Replication and Repair
Essers, J., Theil, A. F., Baldeyron, C., van Cappellen, W. A., Houtsmuller, A. B., Kanaar, R., & Vermeulen, W. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9350-9359.2005 · Cited by 443
ATR phosphorylates SMARCAL1 to prevent replication fork collapsePreprint
Couch, F. B., Bansbach, C. E., Driscoll, R., Luzwick, J. W., Glick, G. G., Betous, R., Carroll, C. M., Jung, S. Y., Qin, J., Cimprich, K. A., et al. (2013) · Genes & Development · doi:10.1101/gad.214080.113 · Cited by 440
A p53-Dependent Checkpoint Pathway Prevents Rereplication
Vaziri, C., Saxena, S., Jeon, Y., Lee, C., Murata, K., Machida, Y., Wagle, N., Hwang, D. S., & Dutta, A. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00099-6 · Cited by 393
Two E3 ubiquitin ligases, SCF‐Skp2 and DDB1‐Cul4, target human Cdt1 for proteolysis
Nishitani, H., Sugimoto, N., Roukos, V., Nakanishi, Y., Saijo, M., Obuse, C., Tsurimoto, T., Nakayama, K., Nakayama, K., Fujita, M., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601002 · Cited by 392
Hanada, K., Budzowska, M., Davies, S. L., van Drunen, E., Onizawa, H., Beverloo, H. B., Maas, A., Essers, J., Hickson, I. D., & Kanaar, R. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1313 · Cited by 392
Georgakopoulou, E., Tsimaratou, K., Evangelou, K., Fernandez, M.-P., Zoumpourlis, V, Trougakos, I., Kletsas, D., Bartek, J., Serrano, M., & Gorgoulis, V. (2012) · Aging · doi:10.18632/aging.100527 · Cited by 390
Self-citationChang, B.-D., Xuan, Y., Broude, E. V., Zhu, H., Schott, B., Fang, J., & Roninson, I. B. (1999) · Oncogene · doi:10.1038/sj.onc.1203078 · Cited by 387
Self-citationMailand, N., & Diffley, J. (2005) · Cell · doi:10.1016/j.cell.2005.08.013 · Cited by 373
Abbas, T., Sivaprasad, U., Terai, K., Amador, V., Pagano, M., & Dutta, A. (2008) · Genes & Development · doi:10.1101/gad.1676108 · Cited by 363
Pathways of mammalian replication fork restart
Petermann, E., & Helleday, T. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2974 · Cited by 340
Marti, A., Wirbelauer, C., Scheffner, M., & Krek, W. (1999) · Nature Cell Biology · doi:10.1038/8984 · Cited by 318
Holland, A. J., & Cleveland, D. W. (2012) · Nature Medicine · doi:10.1038/nm.2988 · Cited by 315
Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells
Viale, A., Franco, F., Orleth, A., Cambiaghi, V., Giuliani, V., Bossi, D., Ronchini, C., Ronzoni, S., Muradore, I., Monestiroli, S., et al. (2008) · Nature · doi:10.1038/nature07618 · Cited by 314
Id proteins in cell growth and tumorigenesis
Sikder, H. A., Devlin, M. K., Dunlap, S., Ryu, B., & Alani, R. M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00141-7 · Cited by 309
Warfel, N. A., & El‐Deiry, W. S. (2012) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32835b639e · Cited by 287
Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangementsPreprint
Zhang, C., Leibowitz, M. L., & Pellman, D. S. (2013) · Genes & Development · doi:10.1101/gad.229559.113 · Cited by 258
Bischoff, F. Z., Yim, S. O., Pathak, S., Grant, G., Siciliano, M. J., Giovanella, B. C., Strong, L. C., & Tainsky, M. A. (1990) · PubMed · Cited by 252
The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing
Kim, Y., Starostina, N. G., & Kipreos, E. T. (2008) · Genes & Development · doi:10.1101/gad.1703708 · Cited by 240
Cyclin-Dependent Kinases and S Phase Control in Mammalian Cells
Woo, R. A., & Poon, R. Y. C. (2003) · Cell Cycle · doi:10.4161/cc.2.4.468 · Cited by 234
Replication licensing and cancer — a fatal entanglement?
Blow, J. J., & Gillespie, P. J. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2500 · Cited by 232
Self-citationMechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligasePreprint
Havens, C. G., & Walter, J. C. (2011) · Genes & Development · doi:10.1101/gad.2068611 · Cited by 228
Deregulated Overexpression of hCdt1 and hCdc6 Promotes Malignant Behavior
Liontos, M., Koutsami, M., Sideridou, M., Evangelou, K., Kletsas, D., Levy, B., Kotsinas, A., Nahum, O., Zoumpourlis, V. C., Kouloukoussa, M., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2837 · Cited by 222
Self-citationGenomic Instability in CancerPreprint
Abbas, T., Keaton, M., & Dutta, A. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012914 · Cited by 206
DNA replication and progression through S phase
Takeda, D. Y., & Dutta, A. (2005) · Oncogene · doi:10.1038/sj.onc.1208616 · Cited by 201
Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function
Schlisio, S., Halperin, T., Vidal, M., & Nevins, J. R. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf577 · Cited by 197
The role of microhomology in genomic structural variation
Ottaviani, D., LeCain, M., & Sheer, D. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.01.001 · Cited by 192
Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates
Neelsen, K. J., Zanini, I. M. Y., Herrador, R., & Lopes, M. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212058 · Cited by 188
Self-citationKarakaidos, P., Taraviras, S. L., Vassiliou, L. V., Zacharatos, P., Kastrinakis, N. G., Kougiou, D., Kouloukoussa, M., Nishitani, H., Papavassiliou, A. G., Lygerou, Z., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63393-7 · Cited by 180
Self-citationChan, J. K. C. (1990) · Histopathology · doi:10.1111/j.1365-2559.1990.tb01104.x · Cited by 180
Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression
Bates, S., Ryan, K. M., Phillips, A. C., & Vousden, K. H. (1998) · Oncogene · doi:10.1038/sj.onc.1202104 · Cited by 176
Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase
Beck, H., Nähse, V., Larsen, M. S. Y., Groth, P., Clancy, T., Lees, M. J., Jørgensen, M., Helleday, T., Syljuåsen, R. G., & Sørensen, C. S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200905059 · Cited by 174
Self-citationp57KIP2: “Kip”ing the Cell under Control
Pateras, I. S., Apostolopoulou, K., Niforou, K., Kotsinas, A., & Gorgoulis, V. G. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0317 · Cited by 159
Self-citationWang, Y., Blandino, G., & Givol, D. (1999) · Oncogene · doi:10.1038/sj.onc.1202632 · Cited by 142
Velimezi, G., Liontos, M., Vougas, K., Roumeliotis, T., Bartkova, J., Sideridou, M., Dereli-Oz, A., Kocylowski, M., Pateras, I. S., Evangelou, K., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2795 · Cited by 131
Self-citationSET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation
Jørgensen, S., Eskildsen, M., Fugger, K., Hansen, L., Larsen, M. S. Y., Kousholt, A. N., Syljuåsen, R. G., Trelle, M. B., Jensen, O. N., Helin, K., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201009076 · Cited by 128
Self-citationCha, H. H., Cram, E. J., Wang, E. C., Huang, A. J., Kasler, H. G., & Firestone, G. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.1998 · Cited by 125
Cytotoxicity and estrogenicity of Invisalign appliances
Eliades, T., Pratsinis, H., Athanasiou, A. E., Eliades, G., & Kletsas, D. (2009) · American Journal of Orthodontics and Dentofacial Orthopedics · doi:10.1016/j.ajodo.2009.03.006 · Cited by 117
Self-citationDNA lesions sequestered in micronuclei induce a local defective-damage response
Terradas, M., Martín, M., Tusell, L., & Genescà, A. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.07.004 · Cited by 110
p53 activates ICAM‐1 (CD54) expression in an NF‐κB‐independent manner
Gorgoulis, V. G., Zacharatos, P., Kotsinas, A., Kletsas, D., Mariatos, G., Zoumpourlis, V., Ryan, K. M., Kittas, C. N., & Papavassiliou, A. G. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg157 · Cited by 103
Self-citationRecovery of Arrested Replication Forks by Homologous Recombination Is Error-Prone
Iraqui, I., Chekkal, Y., Jmari, N., Pietrobon, V., Fréon, K., Costes, A., & Lambert, S. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002976 · Cited by 102
A network of p73, p53 and Egr1 is required for efficient apoptosis in tumor cells
Yu, J., Baron, V. T., Mercola, D., Mustelin, T., & Adamson, E. D. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402029 · Cited by 101
p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes
Benson, E. K., Mungamuri, S. K., Attie, O., Kracikova, M., Sachidanandam, R., Manfredi, J. J., & Aaronson, S. A. (2013) · Oncogene · doi:10.1038/onc.2013.378 · Cited by 100
Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins
Sideridou, M., Zakopoulou, R., Evangelou, K., Liontos, M., Kotsinas, A., Rampakakis, E., Gagos, S., Kahata, K., Grabušić, K., Gkouskou, K. K., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201108121 · Cited by 98
Self-citationDeregulated origin licensing leads to chromosomal breaks by rereplication of a gapped DNA templatePreprint
Neelsen, K. J., Zanini, I. M. Y., Mijic, S., Herrador, R., Zellweger, R., Chaudhuri, A. R., Creavin, K., Blow, J. J., & Lopes, M. (2013) · Genes & Development · doi:10.1101/gad.226373.113 · Cited by 95
Self-citationRad51 Protein Controls Rad52-mediated DNA Annealing
Wu, Y., Kantake, N., Sugiyama, T., & Kowalczykowski, S. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801097200 · Cited by 90
p53-Dependent Regulation of Cdc6 Protein Stability Controls Cellular Proliferation
Duursma, A. M., & Agami, R. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.6937-6947.2005 · Cited by 80
CDK/CK1 inhibitors roscovitine and CR8 downregulate amplified MYCN in neuroblastoma cells
Delehouzé, C., Godl, K., Loaëc, N., Bruyère, C., Desban, N., Oumata, N., Galons, H., Roumeliotis, T. I., Γιαννοπούλου, Ε., Grenet, J. A., et al. (2013) · Oncogene · doi:10.1038/onc.2013.513 · Cited by 70
Self-citationNeelsen, K. J., Chaudhuri, A. R., Follonier, C., Herrador, R., & Lopes, M. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-706-8_15 · Cited by 69
Self-citationEvangelou, K., Bartkova, J., Kotsinas, A., Pateras, I. S., Liontos, M., Velimezi, G., Kosar, M., Liloglou, T., Trougakos, I. P., Dyrskjot, L., et al. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2013.76 · Cited by 59
Self-citationGibbs, E., Kelman, Z., Gulbis, J. M., O’Donnell, M. E., Kuriyan, J., Burgers, P., & Hurwitz, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.4.2373 · Cited by 58
Garbis, S. D., Roumeliotis, T. I., Tyritzis, S. Ι., Zorpas, K. M., Pavlakis, K., & Constantinides, C. A. (2010) · Analytical Chemistry · doi:10.1021/ac102075d · Cited by 55
Self-citationAPC/CCdc20targets E2F1 for degradation in prometaphase
Peart, M. J., Poyurovsky, M. V., Kass, E. M., Urist, M. J., Verschuren, E. W., Summers, M. K., Jackson, P. K., & Prives, C. L. (2010) · Cell Cycle · doi:10.4161/cc.9.19.13162 · Cited by 52
Liontos, M., Niforou, K., Velimezi, G., Vougas, K. N., Evangelou, K., Apostolopoulou, K., Vrtěl, R., Damalas, A. F., Kontovazenitis, P., Kotsinas, A., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.081160 · Cited by 48
Self-citationThe WRN and MUS81 proteins limit cell death and genome instability following oncogene activation
Murfuni, I., Nicolai, S., Baldari, S., Crescenzi, M., Bignami, M., Franchitto, A., & Pichierri, P. (2012) · Oncogene · doi:10.1038/onc.2012.80 · Cited by 48
Exploring and exploiting the systemic effects of deregulated replication licensing
Petrakis, T. G., Komseli, E.-S., Papaioannou, M. D., Vougas, K., Polyzos, A., Myrianthopoulos, V., Mikros, E., Trougakos, I. P., Thanos, D., Branzei, D., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.12.002 · Cited by 46
Self-citationRegulation of E2F1 by APC/CCdh1via K11 linkage-specific ubiquitin chain formation
Budhavarapu, V. N., White, E., Mahanic, C. S., Chen, L., Lin, F., & Lin, W.-C. (2012) · Cell Cycle · doi:10.4161/cc.20643 · Cited by 41
Gorgoulis, V. G., Zacharatos, P., Kotsinas, A., Mariatos, G., Liloglou, T., Vogiatzi, T., Foukas, P., Rassidakis, G. Z., Garinis, G. A., Ioannides, T., et al. (2000) · Molecular Medicine · doi:10.1007/bf03402115 · Cited by 38
Self-citationPreventing DNA over-replication: a Cdk perspective
Porter, A. C. G. (2008) · Cell Division · doi:10.1186/1747-1028-3-3 · Cited by 37
Papachristou, E. K., Roumeliotis, T. I., Chrysagi, A., Trigoni, C., Charvalos, E., Townsend, P. A., Pavlakis, K., & Garbis, S. D. (2013) · Journal of Proteome Research · doi:10.1021/pr301067r · Cited by 35
Self-citationSakellariou, D., Chiourea, M., Raftopoulou, C., & Gagos, S. (2013) · Neoplasia · doi:10.1593/neo.131574 · Cited by 28
Self-citationStatsDB: platform-agnostic storage and understanding of next generation sequencing run metrics
Ramirez-Gonzalez, R. H., Leggett, R. M., Waite, D., Thanki, A. S., Drou, N., Cáccamo, M., & Davey, R. (2013) · F1000Research · doi:10.12688/f1000research.2-248.v1 · Cited by 18
Cited by
Sorted by citations
Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
Self-citationMechanisms 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
Cell cycle regulation: p53-p21-RB signaling
Engeland, K. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00988-z · Cited by 1,367
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
p21: a two-faced genome guardian.
Georgakilas, A. G., Martin, O. A., & Bonner, W. M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.02.001 · Cited by 489
Metadata
- Authors
- Galanos, P., Vougas, K., Walter, D., Polyzos, A., Maya-Mendoza, A., Haagensen, E. J., Kokkalis, A., Roumelioti, F.-M., Gagos, S., Tzetis, M., Canovas, B., Igea, A., Ahuja, A. K., Zellweger, R., Havaki, S., Kanavakis, E., Kletsas, D., Roninson, I. B., Garbis, S. D., Lopes, M., Nebreda, A., Thanos, D., Blow, J. J., Townsend, P., Sørensen, C. S., Bartek, J., & Gorgoulis, V. G.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Biomedical Research Foundation of the Academy of Athens (GR)
- University of Copenhagen (DK)
- University of Dundee (GB)
- Institute for Research in Biomedicine (ES)
- University of Zurich (CH)
- National Centre of Scientific Research "Demokritos" (GR)
- University of South Carolina (US)
- University of Southampton (GB)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Gorgoulis, Vassilis G.
- ORCID
- Galanos, Panagiotis
- Vougas, Konstantinos
- Walter, David
- Polyzos, Alexander
- Haagensen, Emma J.
- Kokkalis, Antonis
- Roumelioti, Fani-Marlen
- Gagos, Sarantis
- Tzetis, Maria
- Igea, Ana
- Ahuja, Akshay K.
- Kletsas, Dimitris
- Roninson, Igor B.
- Garbis, Spiros D.
- Lopes, Massimo
- Thanos, Dimitris
- Blow, J. Julian
- Townsend, Paul
- Sørensen, Claus Storgaard
- Gorgoulis, Vassilis G.
- Venue
- Nature Cell Biology
- Published
- 2016-06-20
- Volume
- 18
- Issue
- 7
- Pages
- 777-789
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC6535144
- OpenAlex
- W2470774921
- Cited by
- 308
- References
- 90
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 35 · 2023: 29 · 2022: 26 · 2021: 40 · 2020: 22 · 2019: 37 · 2018: 25 · 2017: 27 · 2016: 20
- FWCI
- 19.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Funders
- Wellcome Trust (096598, 096598/Z/11/Z, 097945/C/11/Z)
- European Commission (284460)
- General Secretariat for Research and Technology
- Lundbeckfonden (R93-2011-8990)
- Novo Nordisk Fonden (NNF15OC0016584, NNF12OC0002290)
- 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 › DNA Repair Mechanisms
- Keywords
- p21, genomic instability, replication licensing, replication stress, senescence, chemoresistance, tumor aggressiveness, cell proliferation
- MeSH terms
- Cells, Cultured, DNA Replication, Humans, Neoplasms, Tumor Suppressor Protein p53, Cyclins, Genomic Instability, Cyclin-Dependent Kinase Inhibitor p21
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
