Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Open accessAbstract
p21CIP1/WAF1 is a CDK inhibitor regulated by the tumor suppressor p53 and is hypothesized to mediate G1 arrest. p53 has been suggested to derive anti-oncogenic properties from this relationship. To test these notions, we created mice lacking p21CIP1/WAF1. They develop normally and (unlike p53-/- mice) have not developed spontaneous malignancies during 7 months of observation. Nonetheless, p21-/- embryonic fibroblasts are significantly deficient in their ability to arrest in G1 in response to DNA damage and nucleotide pool perturbation. p21-/- cells also exhibit a significant growth alteration in vitro, achieving a saturation density as high as that observed in p53-/- cells. In contrast, other aspects of p53 function, such as thymocytic apoptosis and the mitotic spindle checkpoint, appear normal. These results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and the anti-oncogenic effects of p53 are more complex.
Integrity signals
Registry
Cites
Statistics
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?
p21 is required for p53-mediated G1/S cell cycle arrest.
“p21 is required for p53-mediated G1/S146, 147, 148 and also for G2/M cell cycle arrest.149”
From Census and evaluation of p53 target genes (2017) · cites this paper as [148]
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321 · see citing works
p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018 · see citing works
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
Wade Harper, J. (1993) · Cell · doi:10.1016/0092-8674(93)90499-g · Cited by 5,651 · see citing works
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649 · see citing works
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063 · see citing works
Participation of p53 protein in the cellular response to DNA damage.
Kastan, M. B., Onyekwere, O. C., Sidransky, D., Vogelstein, B., & Craig, R. W. (1991) · PubMed · Cited by 3,761 · see citing works
p21 is a universal inhibitor of cyclin kinases
Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., & Beach, D. (1993) · Nature · doi:10.1038/366701a0 · Cited by 3,691 · see citing works
Inhibitors of mammalian G1 cyclin-dependent kinases.Preprint
Sherr, C. J., & Roberts, J. M. (1995) · Genes & Development · doi:10.1101/gad.9.10.1149 · Cited by 3,222 · see citing works
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047 · see citing works
p53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864 · see citing works
A Single Ataxia Telangiectasia Gene with a Product Similar to PI-3 Kinase
Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., et al. (1995) · Science · doi:10.1126/science.7792600 · Cited by 2,785 · see citing works
Hartwell, L. H., & Kastan, M. B. (1994) · Science · doi:10.1126/science.7997877 · Cited by 2,523 · see citing works
Thymocyte apoptosis induced by p53-dependent and independent pathways
Clarke, A. R., Purdie, C. A., Harrison, D. J., Morris, R. G., Bird, C. C., Hooper, M. L., & Wyllie, A. H. (1993) · Nature · doi:10.1038/362849a0 · Cited by 2,271 · see citing works
p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21.
Toyoshima, H., & Hunter, T. (1994) · Cell · doi:10.1016/0092-8674(94)90573-8 · Cited by 2,208 · see citing works
Polyák, K., Lee, M.-H., Erdjument‐Bromage, H., Koff, A., Roberts, J. M., Tempst, P., & Massagué, J. (1994) · Cell · doi:10.1016/0092-8674(94)90572-x · Cited by 2,118 · see citing works
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051 · see citing works
WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis.
El‐Deiry, W. S., Harper, J. W., O'Connor, P. M., Velculescu, V. E., Ce, C., Jackman, J., Pietenpol, J. A., Burrell, M., De, H., & Wang, Y. (1994) · PubMed · Cited by 2,021 · see citing works
Wild-type p53 is a cell cycle checkpoint determinant following irradiation.
Kuerbitz, S. J., Plunkett, B., Walsh, W., & Kastan, M. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.16.7491 · Cited by 1,837 · see citing works
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801 · see citing works
The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
Waga, S., Hannon, G. J., Beach, D., & Stillman, B. (1994) · Nature · doi:10.1038/369574a0 · Cited by 1,655 · see citing works
Dulić, V., Kaufmann, W. K., Wilson, S. J., Tisty, T. D., Lees, E., Harper, J. W., Elledge, S. J., & Reed, S. I. (1994) · Cell · doi:10.1016/0092-8674(94)90379-4 · Cited by 1,465 · see citing works
Self-citationCloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen
Noda, A., Ning, Y., Venable, S. F., Pereira-Smith, O. M., & Smith, J. R. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1063 · Cited by 1,351 · see citing works
Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53
Livingstone, L. R., White, A., Sprouse, J., Livanos, E., Jacks, T., & Tlsty, T. D. (1992) · Cell · doi:10.1016/0092-8674(92)90243-6 · Cited by 1,333 · see citing works
mdm2 expression is induced by wild type p53 activity.
Barak, Y., Juven, T., Haffner, R., & Oren, M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05678.x · Cited by 1,290 · see citing works
Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T., & Mulligan, R. C. (1991) · Cell · doi:10.1016/0092-8674(91)90011-m · Cited by 1,281 · see citing works
Di Leonardo, A., Linke, S. P., Clarkin, K., & Wahl, G. M. (1994) · Genes & Development · doi:10.1101/gad.8.21.2540 · Cited by 1,215 · see citing works
Human Cyclin E, a Nuclear Protein Essential for the G1-to-S Phase Transition
Ohtsubo, M., Theodoras, A. M., Schumacher, J. M., Roberts, J. M., & Pagano, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.5.2612 · Cited by 1,142 · see citing works
Correlation of Terminal Cell Cycle Arrest of Skeletal Muscle with Induction of p21 by MyoD
Halevy, O., Novitch, B. G., Spicer, D. B., Skapek, S. X., Rhee, J., Hannon, G. J., Beach, D., & Lassar, A. B. (1995) · Science · doi:10.1126/science.7863327 · Cited by 1,139 · see citing works
p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage.Preprint
Macleod, K. F., Sherry, N., Hannon, G. J., Beach, D., Tokino, T., Kinzler, K. W., Vogelstein, B., & Jacks, T. (1995) · Genes & Development · doi:10.1101/gad.9.8.935 · Cited by 1,119 · see citing works
Inhibition of cyclin-dependent kinases by p21.
Harper, J., Elledge, S., Keyomarsi, K., Dynlacht, B., Tsai, L., Zhang, P.-M., Dobrowolski, S., Bai, C., Connell-Crowley, L., & Swindell, E. (1995) · Molecular Biology of the Cell · doi:10.1091/mbc.6.4.387 · Cited by 1,111 · see citing works
Self-citationYin, Y., Tainsky, M. A., Bischoff, F. Z., Strong, L. C., & Wahl, G. M. (1992) · Cell · doi:10.1016/0092-8674(92)90244-7 · Cited by 1,089 · see citing works
Teratocarcinomas and Embryonic Stem Cells: A Practical Approach
Robertson, E. J., & Beddington, R. (1988) · Development · doi:10.1242/dev.102.1.3 · Cited by 1,034 · see citing works
p53-Independent Expression of p21 Cip1 in Muscle and Other Terminally Differentiating Cells
Parker, S. B., Gregor Eichele, C., Zhang, P., Rawls, A., Sands, A., Bradley, A., Olson, E. N., Harper, J. W., & Elledge, S. J. (1995) · Science · doi:10.1126/science.7863329 · Cited by 1,032 · see citing works
Self-citationMatsuoka, S., Edwards, M. C., Bai, C., Parker, S., Zhang, P., Baldini, A., Harper, J. W., & Elledge, S. J. (1995) · Genes & Development · doi:10.1101/gad.9.6.650 · Cited by 952 · see citing works
Self-citationInteraction of the p53-Regulated Protein Gadd45 with Proliferating Cell Nuclear Antigen
Smith, M. L., Chen, I. T., Zhan, Q., Bae, I., Chen, C.-Y., Gilmer, T. M., Kastan, M. B., O'Connor, P. M., & Fornace, A. J. (1994) · Science · doi:10.1126/science.7973727 · Cited by 946 · see citing works
UV Irradiation Stimulates Levels of p53 Cellular Tumor Antigen in Nontransformed Mouse Cells
Maltzman, W., & Czyzyk, L. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.9.1689 · Cited by 893 · see citing works
Lee, M., Reynisdóttir, I., & Massagué, J. (1995) · Genes & Development · doi:10.1101/gad.9.6.639 · Cited by 889 · see citing works
Teratocarcinomas and embryonic stem cells: A practical approach
Krumlauf, R. K. (1987) · Trends in Genetics · doi:10.1016/0168-9525(87)90286-1 · Cited by 779 · see citing works
Murine FGFR-1 is required for early postimplantation growth and axial organization.Preprint
Deng, C.-X., Wynshaw-Boris, A., Shen, M. M., Daugherty, C., Ornitz, D., & Leder, P. (1994) · Genes & Development · doi:10.1101/gad.8.24.3045 · Cited by 775 · see citing works
Self-citationInhibition of CDK2 activity in vivo by an associated 20K regulatory subunit
Gu, Y., Turck, C. W., & Morgan, D. O. (1993) · Nature · doi:10.1038/366707a0 · Cited by 771 · see citing works
Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells
Hartwell, L. H. (1992) · Cell · doi:10.1016/0092-8674(92)90586-2 · Cited by 770 · see citing works
A p53-Dependent Mouse Spindle Checkpoint
Cross, S. M., Sanchez, C. A., Morgan, C. A., Schimke, M. K., Ramel, S., Idzerda, R. L., Raskind, W. H., & Reid, B. J. (1995) · Science · doi:10.1126/science.7871434 · Cited by 660 · see citing works
Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
Gu, Y., Rosenblatt, J., & Morgan, D. O. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05493.x · Cited by 648 · see citing works
Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
Harvey, M., McArthur, M. J., Montgomery, C. A., Butel, J. S., Bradley, A., & Donehower, L. A. (1993) · Nature Genetics · doi:10.1038/ng1193-225 · Cited by 542 · see citing works
Jiang, H., Lin, J., Su, Z., Collart, F., Huberman, E., & Fisher, P. B. (1994) · PubMed · Cited by 495 · see citing works
Wahl, G. M., Padgett, R. A., & Stark, G. R. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)86945-4 · Cited by 481 · see citing works
Induction of p21 (WAF-1/CIP1) during differentiation.
Steinman, R. A., Hoffman‐Liebermann, B., Iro, A., Guillouf, C., Liebermann, D. A., & El-Houseini, M. E. (1994) · PubMed · Cited by 477 · see citing works
Cyclin G is a transcriptional target of the p53 tumor suppressor protein.
Okamoto, K., & Beach, D. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06807.x · Cited by 455 · see citing works
Flores-Rozas, H., Kelman, Z., Dean, F. B., Pan, Z. Q., Harper, J. W., Elledge, S. J., O'Donnell, M., & Hurwitz, J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8655 · Cited by 416 · see citing works
Self-citationCooperative tumorigenic effects of germline mutations in Rb and p53
Williams, B. O., Remington, L., Albert, D. M., Mukai, S., Bronson, R. T., & Jacks, T. (1994) · Nature Genetics · doi:10.1038/ng0894-480 · Cited by 367 · see citing works
Absence of WAF1 mutations in a variety of human malignancies
Shiohara, M., El‐Deiry, W. S., Wada, M., Nakamaki, T., Takeuchi, S., Yang, R., Chen, D., Vogelstein, B., & Koeffler, H. (1994) · Blood · doi:10.1182/blood.v84.11.3781.bloodjournal84113781 · Cited by 366 · see citing works
Growth factor modulation of p53-mediated growth arrest versus apoptosis.Preprint
Canman, C. E., Gilmer, T. M., Coutts, S. B., & Kastan, M. B. (1995) · Genes & Development · doi:10.1101/gad.9.5.600 · Cited by 365 · see citing works
Cdk inhibitors: on the threshold of checkpoints and development
Elledge, S. J., & Harper, J. W. (1994) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(94)90055-8 · Cited by 321 · see citing works
Self-citationLotem, J., & Sachs, L. (1993) · Blood · doi:10.1182/blood.v82.4.1092.1092 · Cited by 300 · see citing works
Evidence for a second cell cycle block at G2/M by p53.
Stewart, N., Hicks, G. G., PARASKEVAS, F., & Mowat, M. R. A. (1995) · PubMed · Cited by 300 · see citing works
Tumour suppressors, kinases and clamps: How p53 regulates the cell cycle in response to DNA damage
Cox, L. S., & Lane, D. P. (1995) · BioEssays · doi:10.1002/bies.950170606 · Cited by 284 · see citing works
Rapid quantitation of apoptosis in pure and heterogeneous cell populations using flow cytometry
Telford, W. G., King, L. E., & Fraker, P. J. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90373-5 · Cited by 240 · see citing works
Elledge, S. J., Richman, R., Hall, F. L., Williams, R. T., Lodgson, N., & Harper, J. W. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.7.2907 · Cited by 224 · see citing works
Self-citationSwyryd, E. A., Seaver, S. S., & Stark, G. R. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42149-2 · Cited by 213 · see citing works
Hinds, P. W., & Weinberg, R. A. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90102-3 · Cited by 207 · see citing works
Multiple members of the E2F transcription factor family are the products of oncogenes.
Xu, G., Livingston, D. M., & Krek, W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.5.1357 · Cited by 194 · see citing works
Strasser, A., Harris, A. W., & Cory, S. (1993) · PubMed · Cited by 165 · see citing works
Expression of Wild-Type p53 Is Not Compatible with - Continued Growth of p53-Negative Tumor Cells
Johnson, P., Gray, D. A., Mowat, M. R. A., & Benchimol, S. (1991) · Molecular and Cellular Biology · doi:10.1128/mcb.11.1.1 · Cited by 114 · see citing works
Aloni-Grinstein, R., Schwartz, D., & Rotter, V. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07125.x · Cited by 105 · see citing works
Noguchi, E., Sekiguchi, T., Yamashita, K., & Nishimoto, T. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2650 · Cited by 17 · see citing works
Flagged first, then by citations
5 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693 · see citing works
CDK inhibitors: positive and negative regulators of G1-phase progression
Sherr, C. J., & Roberts, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.12.1501 · Cited by 6,115 · see citing works
Sherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379 · see citing works
HOW CELLS RESPOND TO INTERFERONS
Stark, G. R., Kerr, I. M., Williams, B. R. G., Silverman, R. H., & Schreiber, R. D. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.227 · Cited by 3,932 · see citing works
Requirement for p53 and p21 to Sustain G <sub>2</sub> Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803 · see citing works
A microRNA component of the p53 tumour suppressor network
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007) · Nature · doi:10.1038/nature05939 · Cited by 2,692 · see citing works
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712 · see citing works
p53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,338 · see citing works
PUMA, a Novel Proapoptotic Gene, Is Induced by p53
Nakano, K., & Vousden, K. H. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00214-3 · Cited by 2,315 · see citing works
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., & Giaccia, A. J. (1996) · Nature · doi:10.1038/379088a0 · Cited by 2,300 · see citing works
Yang, A., Kaghad, M., Wang, Y., Gillett, E. S., Fleming, M. D., Dötsch, V., Andrews, N. C., Caput, D., & McKeon, F. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80275-0 · Cited by 2,086 · see citing works
The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer
Vermeulen, K., Bockstaele, D. R. V., & Berneman, Z. N. (2003) · Cell Proliferation · doi:10.1046/j.1365-2184.2003.00266.x · Cited by 1,766 · see citing works
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712 · 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
Nakayama, K., Ishida, N., Shirane, M., Inomata, A., Inoue, T., SHISHIDO, N., Horii, I., Loh, D. Y., & Nakayama, K. (1996) · Cell · doi:10.1016/s0092-8674(00)81237-4 · Cited by 1,548 · see citing works
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,450 · see citing works
Fero, M. L., Rivkin, M. J., Tasch, M., Porter, P. L., Carow, C. E., Firpo, E. J., Polyák, K., Tsai, L., Broudy, V. C., Perlmutter, R. M., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81239-8 · Cited by 1,459 · see citing works
How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.169 · Cited by 1,395 · see citing works
New functional activities for the p21 family of CDK inhibitors.
LaBaer, J., Garrett, M. D., Stevenson, L. F., Slingerland, J. M., Sandhu, C., Chou, H. S., Fattaey, A., & Harlow, E. (1997) · Genes & Development · doi:10.1101/gad.11.7.847 · Cited by 1,402 · see citing works
Unravelling mechanisms of p53-mediated tumour suppression
Bieging-Rolett, K. T., Mello, S. S., & Attardi, L. D. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3711 · Cited by 1,389 · see citing works
Hematopoietic Stem Cell Quiescence Maintained by p21 <sup>cip1/waf1</sup>
Cheng, T., Rodrigues, N., Shen, H., Yang, Y.-G., Dombkowski, D., Sykes, M., & Scadden, D. T. (2000) · Science · doi:10.1126/science.287.5459.1804 · Cited by 1,339 · see citing works
Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., & Elledge, S. J. (1997) · Science · doi:10.1126/science.277.5331.1497 · Cited by 1,320 · see citing works
Self-citationLife, death, and the pursuit of apoptosis.Preprint
White, E. (1996) · Genes & Development · doi:10.1101/gad.10.1.1 · Cited by 1,300 · see citing works
Cell cycle regulation: p53-p21-RB signaling
Engeland, K. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00988-z · Cited by 1,308 · see citing works
The codon 72 polymorphic variants of p53 have markedly different apoptotic potential
Dumont, P., Leu, J. I.-J., Pietra, A. D., George, D. L., & Murphy, M. E. (2003) · Nature Genetics · doi:10.1038/ng1093 · Cited by 1,269 · see citing works
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222 · see citing works
Is a p53-Regulated Inhibitor of G2/M Progression
Hermeking, H., Lengauer, C., Polyak, K., He, T.-C., Zhang, L., Thiagalingam, S., Kinzler, K. W., & Vogelstein, B. (1997) · Molecular Cell · doi:10.1016/s1097-2765(00)80002-7 · Cited by 1,251 · see citing works
Senescence is a developmental mechanism that contributes to embryonic growth and patterning
Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.041 · Cited by 1,186 · see citing works
Living on a break: cellular senescence as a DNA-damage response
d'Adda di Fagagna, F. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2440 · Cited by 1,170 · see citing works
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
Caveolin-1 Null Mice Are Viable but Show Evidence of Hyperproliferative and Vascular Abnormalities
Razani, B., Engelman, J. A., Wang, X., Schubert, W., Zhang, X. L., Marks, C. B., Macaluso, F., Russell, R. G., Li, M., Pestell, R. G., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105408200 · Cited by 1,163 · see citing works
CDK inhibitors: Cell cycle regulators and beyond
Besson, A., Dowdy, S. F., & Roberts, J. M. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.013 · Cited by 1,152 · see citing works
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 · see citing works
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104 · see citing works
The antioxidant function of the p53 tumor suppressor
Sablina, A. A., Budanov, A. V., Ilyinskaya, G. V., Agapova, L. S., Kravchenko, J. E., & Chumakov, P. M. (2005) · Nature Medicine · doi:10.1038/nm1320 · Cited by 1,110 · see citing works
The Death Domain Kinase RIP Mediates the TNF-Induced NF-κB Signal
Kelliher, M. A., Grimm, S., Ishida, Y., Kuo, F., Stanger, B. Z., & Leder, P. (1998) · Immunity · doi:10.1016/s1074-7613(00)80535-x · Cited by 1,102 · see citing works
Self-citationp53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080 · see citing works
Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells
Maddocks, O. D. K., Berkers, C. R., Mason, S. M., Zheng, L., Blyth, K., Gottlieb, E., & Vousden, K. H. (2013) · Nature · doi:10.1038/nature11743 · Cited by 1,007 · see citing works
Disruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044 · see citing works
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971 · see citing works
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979 · see citing works
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., & Gu, W. (2012) · Cell · doi:10.1016/j.cell.2012.04.026 · Cited by 912 · see citing works
The role of the cyclin-dependent kinase inhibitor p21 in apoptosis.
Gartel, A. L., & Tyner, A. L. (2002) · PubMed · Cited by 918 · see citing works
A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage
Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., & Nakamura, Y. (2000) · Nature · doi:10.1038/35003506 · Cited by 904 · see citing works
Cyclin E-CDK2 is a regulator of p27Kip1.Preprint
Sheaff, R. J., Groudine, M. T., Gordon, M., Roberts, J., & Clurman, B. E. (1997) · Genes & Development · doi:10.1101/gad.11.11.1464 · Cited by 910 · see citing works
p53 Activates the CD95 (APO-1/Fas) Gene in Response to DNA Damage by Anticancer Drugs
Müller, M., Wilder, S., Bannasch, D., Israeli, D., Lehlbach, K., Li-Weber, M., Friedman, S. L., Galle, P. R., Stremmel, W., Oren, M., et al. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.11.2033 · Cited by 878 · see citing works
Liu, M., Lee, M., Cohen, M. B., Bommakanti, M., & Freedman, L. P. (1996) · Genes & Development · doi:10.1101/gad.10.2.142 · Cited by 889 · see citing works
Puma is an essential mediator of p53-dependent and -independent apoptotic pathways
Jeffers, J. R., Parganas, E., Lee, Y., Yang, C., Wang, J., Brennan, J. A., Maclean, K. H., Han, J., Chittenden, T., Ihle, J. N., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00244-7 · Cited by 880 · see citing works
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
Matsuoka, S., Rotman, G., Ogawa, A., Shiloh, Y., Tamai, K., & Elledge, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190030497 · Cited by 830 · see citing works
Self-citationThe Mammalian Ovary from Genesis to Revelation
Edson, M. A., Nagaraja, A. K., & Matzuk, M. M. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0012 · Cited by 828 · see citing works
Xu, X., Ohler, Z. W., Linke, S. P., Li, C., Gotay, J., Wang, X. W., Harris, C. C., Ried, T., & Deng, C. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80466-9 · Cited by 819 · see citing works
Self-citationBrown, J. P., Wei, W., & Sedivy, J. M. (1997) · Science · doi:10.1126/science.277.5327.831 · Cited by 804 · see citing works
Regulation ofp53downstream genes
El‐Deiry, W. S. (1998) · Seminars in Cancer Biology · doi:10.1006/scbi.1998.0097 · Cited by 797 · see citing works
Transcriptional Repression of the Anti-apoptoticsurvivin Gene by Wild Type p53
Hoffman, W. H., Biade, S., Zilfou, J. T., Chen, J., & Murphy, M. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m106643200 · Cited by 794 · see citing works
Rapid Destruction of Human Cdc25A in Response to DNA Damage
Mailand, N., Falck, J., Lukas, C., Syljuåsen, R. G., Welcker, M., Bartek, J., & Lukas, J. (2000) · Science · doi:10.1126/science.288.5470.1425 · Cited by 787 · see citing works
Zhang, P., Liégeois, N. J., Wong, C., Finegold, M. J., Hou, H., Thompson, J. C., Silverman, A., Harper, J. W., DePinho, R. A., & Elledge, S. J. (1997) · Nature · doi:10.1038/387151a0 · Cited by 750 · see citing works
Self-citationChen, X., Ko, L. J., Jayaraman, L., & Prives, C. (1996) · Genes & Development · doi:10.1101/gad.10.19.2438 · Cited by 735 · see citing works
Agarwal, M. L., Taylor, W. R., Chernov, M. V., Chernova, O. B., & Stark, G. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.1 · Cited by 725 · see citing works
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 · see citing works
Drugging the p53 pathway: understanding the route to clinical efficacy
Khoo, K. H., Verma, C. S., & Lane, D. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4236 · Cited by 723 · see citing works
Cyclins and cell cycle checkpoints.
Johnson, D. G., & Walker, C. (1999) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.39.1.295 · Cited by 789 · see citing works
Lim, D., & Hasty, P. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.12.7133 · Cited by 687 · see citing works
The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse.
Hakem, R., de la Pompa, J. L., Sirard, C., Mo, R., Woo, M., Hakem, A., Wakeham, A., Potter, J., Reitmair, A., Billia, F., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81302-1 · Cited by 680 · see citing works
Berthet, C., Aleem, E. A., Coppola, V., Tessarollo, L., & Kaldis, P. (2003) · Current Biology · doi:10.1016/j.cub.2003.09.024 · Cited by 665 · see citing works
Transcriptional regulation of the p21((WAF1/CIP1)) gene.
Gartel, A., & Tyner, A. (1999) · Experimental Cell Research · doi:10.1006/excr.1998.4319 · Cited by 735 · see citing works
Twenty years of p53 research: structural and functional aspects of the p53 protein
May, P., & May, E. (1999) · Oncogene · doi:10.1038/sj.onc.1203285 · Cited by 663 · see citing works
The P53 pathway: what questions remain to be explored?
Levine, A. J., Hu, W., & Feng, Z. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401910 · Cited by 654 · see citing works
Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM
Engeland, K. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.172 · Cited by 656 · see citing works
GADD45 induction of a G <sub>2</sub> /M cell cycle checkpoint
Wang, X. W., Zhan, Q., Coursen, J. D., Khan, M. A., Kontny, H. U., Yu, L., Hollander, M. C., O’Connor, P. M., Fornace, A. J., & Harris, C. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3706 · Cited by 634 · see citing works
Woods, D. B., Parry, D., Cherwinski, H. M., Bosch, E., Lees, E. M., & McMahon, M. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.9.5598 · Cited by 639 · see citing works
Molecular mechanisms underlying ErbB2/HER2 action in breast cancer
Harari, D., & Yarden, Y. (2000) · Oncogene · doi:10.1038/sj.onc.1203973 · Cited by 636 · see citing works
Involvement of Brca2 in DNA Repair
Patel, K. J., Yu, V. P. C. C., Lee, H., Corcoran, A. E., Thistlethwaite, F. C., Evans, M. J., Colledge, W. H., Friedman, L. S., Ponder, B. A. J., & Venkitaraman, A. R. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80035-0 · Cited by 631 · see citing works
Paulovich, A. G., Toczyski, D. P., & Hartwell, L. H. (1997) · Cell · doi:10.1016/s0092-8674(00)81870-x · Cited by 625 · see citing works
Andrés, V., & Walsh, K. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.132.4.657 · Cited by 621 · see citing works
Schafer, K. A. (1998) · Veterinary Pathology · doi:10.1177/030098589803500601 · Cited by 609 · see citing works
The cellular response to p53: the decision between life and death
Sionov, R. V., & Haupt, Y. (1999) · Oncogene · doi:10.1038/sj.onc.1203130 · Cited by 600 · see citing works
tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors
Berghmans, S., Murphey, R. D., Wienholds, E., Neuberg, D. S., Kutok, J. L., Fletcher, C. D. �., Morris, J. P., Liu, T. X., Schulte‐Merker, S., Kanki, J. P., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406252102 · Cited by 599 · see citing works
Transcriptional Cross Talk between NF-κB and p53
Webster, G. A., & Perkins, N. D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3485 · Cited by 598 · see citing works
Rowland, B. D., Bernards, R., & Peeper, D. S. (2005) · Nature Cell Biology · doi:10.1038/ncb1314 · Cited by 583 · see citing works
Regulation of G1 cyclin-dependent kinases in the mammalian cell cycle
Ekholm, S. V., & Reed, S. I. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00151-4 · Cited by 587 · see citing works
BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution
Deng, C. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl010 · Cited by 583 · see citing works
Self-citationKriwacki, R. W., Hengst, L., Tennant, L. L., Reed, S. I., & Wright, P. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11504 · Cited by 576 · see citing works
Tumor Suppressive Functions of p53Preprint
Zilfou, J. T., & Lowe, S. W. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001883 · Cited by 610 · see citing works
Structure of the p53 Tumor Suppressor Bound to the Ankyrin and SH3 Domains of 53BP2
Gorina, S. S., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.1001 · Cited by 571 · see citing works
KLF4, p21 and context-dependent opposing forces in cancer
Rowland, B. D., & Peeper, D. S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1780 · Cited by 548 · see citing works
'Super p53' mice exhibit enhanced DNA damage response, are tumor resistant and age normally
García‐Cao, I., García‐Cao, M., Martín‐Caballero, J., Criado, L. M., Klatt, P., Flores, J. M., Weill, J., Blasco, M. A., & Serrano, M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf595 · Cited by 529 · see citing works
HuR Regulates p21 mRNA Stabilization by UV Light
Wang, W., Furneaux, H., Cheng, H., Caldwell, M. C., Hutter, D., Liu, Y., Holbrook, N. J., & Gorospe, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.3.760-769.2000 · Cited by 539 · see citing works
Linke, S. P., Clarkin, K., Leonardo, A. D., Tsou, A.-P., & Wahl, G. M. (1996) · Genes & Development · doi:10.1101/gad.10.8.934 · Cited by 531 · see citing works
Fiscella, M., Zhang, H., Fan, S., Sakaguchi, K., Shen, S., Mercer, W. E., Woude, G. F. V., O'Connor, P. M., & Appella, E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.12.6048 · Cited by 527 · see citing works
Shackelford, R. E., Kaufmann, W. K., & Paules, R. S. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00224-0 · Cited by 520 · see citing works
Funk, J. O., Waga, S., Harry, J. B., Espling, E., Stillman, B., & Galloway, D. A. (1997) · Genes & Development · doi:10.1101/gad.11.16.2090 · Cited by 515 · see citing works
Genomic instability in Gadd45a-deficient mice
Hollander, M. C., Sheikh, M. S., Bulavin, D. V., Lundgren, K., Augeri-Henmueller, L., Shehee, R., Molinaro, T. A., Kim, K. E., Tolosa, E., Ashwell, J. D., et al. (1999) · Nature Genetics · doi:10.1038/13802 · Cited by 507 · see citing works
Self-citationHuang, M., Zhou, Z., & Elledge, S. J. (1998) · Cell · doi:10.1016/s0092-8674(00)81601-3 · Cited by 499 · see citing works
Self-citationCharacterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption
Lanni, J. S., & Jacks, T. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.1055 · Cited by 493 · see citing works
Yan, Y., Frisén, J., Lee, M., Massagué, J., & Barbacid, M. (1997) · Genes & Development · doi:10.1101/gad.11.8.973 · Cited by 491 · 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 · see citing works
Nuclear FAK Promotes Cell Proliferation and Survival through FERM-Enhanced p53 Degradation
Lim, S., Chen, X. L., Lim, Y., Hanson, D. A., Vo, T.-T. T., Howerton, K., Larocque, N., Fisher, S. J., Schlaepfer, D. D., & Ilić, D. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.11.031 · Cited by 483 · see citing works
p53 in growth control and neoplasia
Gottlieb, T. M., & Oren, M. (1996) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(95)00019-c · Cited by 481 · see citing works
Drosophila p53 Binds a Damage Response Element at the reaper Locus
Brodsky, M. H., Nordstrom, W., Tsang, G., Kwan, E., Rubin, G. M., & Abrams, J. (2000) · Cell · doi:10.1016/s0092-8674(00)80627-3 · Cited by 467 · see citing works
- Authors
- Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P.
- Affiliations
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1995-08
- Volume
- 82
- Issue
- 4
- Pages
- 675-684
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2044057392
- Cited by
- 2,113
- References
- 70
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 32 · 2023: 32 · 2022: 34 · 2021: 40 · 2020: 38 · 2019: 40 · 2018: 43 · 2017: 36 · 2016: 37 · 2015: 34 · 2014: 57 · 2013: 39 · 2012: 65
- FWCI
- 61.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute on Aging (AG11085, R01AG011085)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p21, p53, G1/S checkpoint, cyclin-dependent kinase inhibitors, DNA damage response, embryonic fibroblasts, cell growth, thymocyte apoptosis, mitotic spindle checkpoint, tumor suppression
- MeSH terms
- Animals, Base Sequence, Cell Differentiation, Cell Division, Cell Line, DNA, DNA Damage, Spindle Apparatus, Molecular Sequence Data, Neoplasms, Experimental, Genes, p53, Tumor Suppressor Protein p53, G1 Phase, Cyclins, Apoptosis, Cyclin-Dependent Kinase Inhibitor p21, Mice
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