PML is induced by oncogenic ras and promotes premature senescence
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Oncogenic ras provokes a senescent-like arrest in human diploid fibroblasts involving the Rb and p53 tumor suppressor pathways. To further characterize this response, we compared gene expression patterns between ras-arrested and quiescent IMR90 fibroblasts. One of the genes up-regulated during ras-induced arrest was promyelocytic leukemia (PML) protein, a potential tumor suppressor that encodes a component of nuclear structures known as promyelocytic oncogenic domains (PODs). PML levels increased during both ras-induced arrest and replicative senescence, leading to a dramatic increase in the size and number of PODs. Forced PML expression was sufficient to promote premature senescence. Like oncogenic ras, PML increased the levels of p16, hypophosphorylated Rb, phosphoserine-15 p53, and expression of p53 transcriptional targets. The fraction of Rb and p53 that colocalized with PML markedly increased during ras-induced arrest, and expression of PML alone forced p53 to the PODs. E1A abolished PML-induced arrest and prevented PML induction and p53 phosphorylation in response to oncogenic ras. These results imply that PML acts with Rb and p53 to promote ras-induced senescence and provide new insights into PML regulation and activity.
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Senescence in human diploid fibroblasts involves the combined activities of the p16/Rb pathway, p53, and PML.
“We have proposed that senescence in human diploid fibroblasts involves the combined activities of the p16/Rb pathway, p53, and the promyelocytic leukemia protein (PML) (Ferbeyre et al., 2000)”
From Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence (2003) · cites this paper as Ferbeyre et al., 2000
The p53 pathway is important for the senescence response to overexpressed oncogenes such as activated RAS.
“The p53 pathway is also important for the senescence response to overexpressed oncogenes such as activated RAS (Serrano et al., 1997; Ferbeyre et al., 2000; Pearson et al., 2000).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Ferbeyre et al., 2000
E1A inhibits p53 phosphorylation at serine 15.
“In particular, E1A inhibits p53 phosphorylation at serine 15 (14), a hallmark of the activation of the DNA damage response during senescence (3, 12).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [14]
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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 · see citing works
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876 · see citing works
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · cited 29× · see citing works
“As a consequence, murine cells lacking p53 are transformed by oncogenic ras, whereas inactivation of p53 in human cells does not rescue ras-induced arrest (Serrano et al. 1997).”
BackgroundMethodResultInfluentialSelf-citationInduction of apoptosis in fibroblasts by c-myc protein
Evan, G. I., Wyllie, A. H., Gilbert, C. S., Littlewood, T. D., Land, H., Brooks, M. W., Waters, C. M., Penn, L. Z., & Hancock, D. C. (1992) · Cell · doi:10.1016/0092-8674(92)90123-t · Cited by 2,941 · see citing works
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
Lowe, S. W., Ruley, H. E., Jacks, T., & Housman, D. E. (1993) · Cell · doi:10.1016/0092-8674(93)90719-7 · Cited by 2,911 · see citing works
Self-citationCreation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345 · see citing works
The regulation of E2F by pRB-family proteins.
Dyson, N. (1998) · Genes & Development · doi:10.1101/gad.12.15.2245 · Cited by 2,317 · see citing works
DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
Shieh, S.-Y., Ikeda, M., Taya, Y., & Prives, C. (1997) · Cell · doi:10.1016/s0092-8674(00)80416-x · Cited by 2,100 · see citing works
Self-citationTumor 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
Kakizuka, A., Miller, W. H., Umesono, K., Warrell, R. P., Frankel, S., Murty, V. V. V. S., Dmitrovsky, E., & Evans, R. M. (1991) · Cell · doi:10.1016/0092-8674(91)90112-c · Cited by 1,423 · see citing works
Whyte, P., Buchkovich, K. J., Horowitz, J. M., Friend, S. H., Raybuck, M., Weinberg, R. A., & Harlow, E. (1988) · Nature · doi:10.1038/334124a0 · Cited by 1,403 · see citing works
Cloning 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
de Thé, H., Lavau, C., Marchio, A., Chomienne, C., Degos, L., & Dejean, A. (1991) · Cell · doi:10.1016/0092-8674(91)90113-d · Cited by 1,331 · see citing works
The complexity of p53 modulation: emerging patterns from divergent signalsPreprint
Giaccia, A. J., & Kastan, M. B. (1998) · Genes & Development · doi:10.1101/gad.12.19.2973 · Cited by 1,303 · see citing works
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
Melnick, A. M., & Licht, J. D. (1999) · Blood · doi:10.1182/blood.v93.10.3167.410k44_3167_3215 · Cited by 1,024 · see citing works
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945 · see citing works
Self-citationSenescence of human fibroblasts induced by oncogenic Raf
Zhu, J., Woods, D., McMahon, M., & Bishop, J. M. (1998) · Genes & Development · doi:10.1101/gad.12.19.2997 · Cited by 826 · see citing works
DNA damage induces phosphorylation of the amino terminus of p53
Siliciano, J. D., Canman, C. E., Taya, Y., Sakaguchi, K., Appella, E., & Kastan, M. B. (1997) · Genes & Development · doi:10.1101/gad.11.24.3471 · Cited by 818 · see citing works
Absence of cancer–associated changes in human fibroblasts immortalized with telomerase
Morales, C. P., Holt, S. E., Ouellette, M. M., Kaur, K. J., Yan, Y., Wilson, K. S., White, M. A., Wright, W. E., & Shay, J. W. (1999) · Nature Genetics · doi:10.1038/5063 · Cited by 805 · see citing works
A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein
Dyck, J. A., Maul, G. G., Miller, W. H., Chen, J. D., Kakizuka, A., & Evans, R. M. (1994) · Cell · doi:10.1016/0092-8674(94)90340-9 · Cited by 783 · see citing works
Microarray analysis of replicative senescence
Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80420-5 · Cited by 764 · see citing works
Binding and modulation of p53 by p300/CBP coactivators
Lill, N. L., Grossman, S. R., Ginsberg, D., DeCaprio, J. A., & Livingston, D. M. (1997) · Nature · doi:10.1038/42981 · Cited by 693 · see citing works
Sherr, C. J., & Weber, J. D. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00038-6 · Cited by 654 · see citing works
Weis, K., Rambaud, S., Lavau, C., Jansen, J. H., Carvalho, T., Carmo‐Fonseca, M., Lamond, A. I., & Dejean, A. (1994) · Cell · doi:10.1016/0092-8674(94)90341-7 · Cited by 646 · see citing works
Prives, C. (1998) · Cell · doi:10.1016/s0092-8674(00)81774-2 · Cited by 623 · see citing works
Self-citationp19ARF links the tumour suppressor p53 to Ras
Palmero, I., Pantoja, C., & Serrano, M. (1998) · Nature · doi:10.1038/25870 · Cited by 617 · see citing works
E1A signaling to p53 involves the p19ARFtumor suppressorPreprint
de Stanchina, E., McCurrach, M. E., Zindy, F., Shieh, S.-Y., Ferbeyre, G., Samuelson, A. V., Prives, C. L., Roussel, M. F., Sherr, C. J., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.15.2434 · Cited by 607 · see citing works
Self-citationThe transcriptional role of PML and the nuclear body
Zhong, S., Salomoni, P., & Pandolfi, P. P. (2000) · Nature Cell Biology · doi:10.1038/35010583 · Cited by 576 · see citing works
(1999) · PubMed · Cited by 546 · see citing works
The biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538 · see citing works
Role of PML in Cell Growth and the Retinoic Acid Pathway
Wang, Z. G., Delva, L., Gaboli, M. P., Rivi, R., Giorgio, M., Cordon‐Cardo, C., Grosveld, F. G., & Pandolfi, P. P. (1998) · Science · doi:10.1126/science.279.5356.1547 · Cited by 516 · see citing works
Cooperation of Stat2 and p300/CBP in signalling induced by interferon-α
Bhattacharya, S., Eckner, R., Grossman, S., Oldread, E., Arany, Z., D'Andrea, A., & Livingston, D. M. (1996) · Nature · doi:10.1038/383344a0 · Cited by 493 · see citing works
Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M. S., Aizawa, S., Mak, T. W., & Taniguchi, T. (1994) · Cell · doi:10.1016/0092-8674(94)90132-5 · Cited by 491 · see citing works
Characterization of a Zinc Finger Gene Disrupted by the t(15;17) in Acute Promyelocytic Leukemia
Goddard, A. D., Borrow, J., Freemont, P. S., et al. (1991) · Science · doi:10.1126/science.1720570 · Cited by 472 · see citing works
Dumaz, N., & Meek, D. W. (1999) · The EMBO Journal · doi:10.1093/emboj/18.24.7002 · Cited by 455 · see citing works
Chang, B.-D., Watanabe, K., Broude, E. V., Fang, J., Poole, J. C., Kalinichenko, T. V., & Roninson, I. B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4291 · Cited by 432 · see citing works
Phosphorylation of p53 Serine 15 Increases Interaction with CBP
Lambert, P. F., Kashanchi, F., Radonovich, M. F., Shiekhattar, R., & Brady, J. N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.49.33048 · Cited by 423 · see citing works
Kastner, P., Perez, A., Lutz, Y., Rochette‐Egly, C., Gaub, M. P., Durand, B., Lanotte, M., Berger, R., & Chambon, P. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05095.x · Cited by 415 · see citing works
Dimri, G. P., Itahana, K., Acosta, M., & Campisi, J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.1.273-285.2000 · Cited by 393 · see citing works
McCurrach, M. E., Connor, T. M. F., Knudson, C. M., Korsmeyer, S. J., & Lowe, S. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2345 · Cited by 368 · see citing works
Self-citationThe Tumor Suppressor Protein p16INK4a
Serrano, M. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3824 · Cited by 346 · see citing works
CDC25A Phosphatase Is a Target of E2F and Is Required for Efficient E2F-Induced S Phase
Vigo, E., Müller, H., Prosperini, E., Hateboer, G., Cartwright, P., Moroni, M. C., & Helin, K. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6379 · Cited by 326 · see citing works
A critical role for telomeres in suppressing and facilitating carcinogenesis
Artandi, S. E., & DePinho, R. A. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00047-7 · Cited by 318 · see citing works
McConnell, B. B., Starborg, M., Brookes, S., & Peters, G. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70137-x · Cited by 314 · see citing works
Wild-type p53 triggers a rapid senescence program in human tumor cells lacking functional p53
Sugrue, M. M., Shin, D. Y., Lee, S. W., & Aaronson, S. A. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9648 · Cited by 290 · see citing works
PML, a Growth Suppressor Disrupted in Acute Promyelocytic Leukemia
Mu, Z. M., Chin, K., Liu, H., Lozano, G., & Chang, K. S. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6858 · Cited by 288 · see citing works
Stadler, M., Chelbi‐Alix, M. K., Koken, M. H. M., Venturini, L., Lee, C., Saı̈b, A., Quignon, F., Pelicano, L., Guillemin, M.-C., & Schindler, C. (1995) · PubMed · Cited by 266 · see citing works
Localization of nascent RNA and CREB binding protein with the PML-containing nuclear body
LaMorte, V. J., Dyck, J. A., Ochs, R., & Evans, R. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.4991 · Cited by 239 · see citing works
Millis, A. J. T., Hoyle, M., McCue, H. M., & Martini, H. (1992) · Experimental Cell Research · doi:10.1016/0014-4827(92)90286-h · Cited by 239 · see citing works
The acute promyelocytic leukaemia-associated PML gene is induced by interferon.
Lavau, C., Marchio, A., Fagioli, M., Jansen, J. H., Falini, B., Lebon, P., Grosveld, F. G., Pandolfi, P. P., Pelicci, P. G., & Dejean, A. (1995) · PubMed · Cited by 228 · see citing works
Webley, K., Bond, J. A., Jones, C. J., Blaydes, J. P., Craig, A., Hupp, T., & Wynford-Thomas, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2803-2808.2000 · Cited by 192 · see citing works
Doucas, V., Tini, M., Egan, D. A., & Evans, R. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.2627 · Cited by 168 · see citing works
The Promyelocytic Leukemia Gene Product (PML) Forms Stable Complexes with the Retinoblastoma Protein
Alcalay, M., Tomassoni, L., Colombo, E., Stoldt, S., Grignani, F., Fagioli, M., Székely, L., Helin, K., & Pelicci, P. G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.1084 · Cited by 160 · see citing works
Korioth, F., Gieffers, C., Maul, G. G., et al. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.130.1.1 · Cited by 157 · see citing works
IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis
Guldner, H. H., Szostecki, C., Grötzinger, T., & Will, H. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.149.12.4067 · Cited by 156 · see citing works
Cellular Response to Oncogenic Ras Involves Induction of the Cdk4 and Cdk6 Inhibitor p15INK4b
Malumbres, M., de Castro, I. P., Hernández, M. I., Jiménez, M., Corral, T., & Pellicer, À. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.8.2915-2925.2000 · Cited by 154 · see citing works
Laín, S., Midgley, C., Sparks, A., Lane, E., & Lane, D. P. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4433 · Cited by 144 · see citing works
p53 mediates permanent arrest over multiple cell cycles in response to gamma-irradiation.
Linke, S. P., Clarkin, K., & Wahl, G. M. (1997) · PubMed · Cited by 143 · see citing works
Induction of senescence in human malignant glioma cells by p16INK4A
Uhrbom, L., Nistér, M., & Westermark, B. (1997) · Oncogene · doi:10.1038/sj.onc.1201227 · Cited by 133 · see citing works
Vogt, M., Haggblom, C., Yeargin, J., Christiansen-Weber, T. A., & Haas, M. (1998) · PubMed · Cited by 124 · see citing works
Nozawa, H., Oda, E., Nakao, K., Ishihara, M., Ueda, S., Yokochi, T., Ogasawara, K., Nakatsuru, Y., SHIMIZU, S., Ohira, Y., et al. (1999) · Genes & Development · doi:10.1101/gad.13.10.1240 · Cited by 120 · see citing works
Sistonen, L., Hölttä, E., Mäkelä, T. P., Keski‐Oja, J., & Alitalo, K. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03442.x · Cited by 109 · see citing works
Repression of the interferon signal transduction pathway by the adenovirus E1A oncogene.
Gutch, M. J., & Reich, N. C. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.18.7913 · Cited by 108 · see citing works
Samuelson, A. V., & Lowe, S. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.22.12094 · Cited by 102 · see citing works
Self-citationWang, Y., Blandino, G., Oren, M., & Givol, D. (1998) · Oncogene · doi:10.1038/sj.onc.1202113 · Cited by 102 · see citing works
PML, a Growth Suppressor Disrupted in Acute Promyelocytic Leukemia
Mu, Z., Chin, K., Liu, H., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.6858-6867.1994 · Cited by 75 · see citing works
Yang, X., He, Z., Xin, B., & Cao, L. (2000) · Oncogene · doi:10.1038/sj.onc.1203515 · Cited by 71 · see citing works
Goldstein, S., Moerman, E. J., Fujii, S., & Sobel, B. E. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041610321 · Cited by 59 · see citing works
Mu, X., & Higgins, P. J. (1995) · Journal of Cellular Physiology · doi:10.1002/jcp.1041650324 · Cited by 56 · see citing works
Jiang, W. Q., & Ringertz, N. R. (1997) · PubMed · Cited by 34 · see citing works
Expression of interleukin-1α and β in early passage fibroblasts from aging individuals
Kumar, S., Vinci, J. M., Millis, A. J. T., & Baglioni, C. (1993) · Experimental Gerontology · doi:10.1016/0531-5565(93)90039-g · Cited by 27 · see citing works
Wong, G. H., & Goeddel, D. V. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)34091-9 · Cited by 4 · see citing works
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- Chang, B.D., Watanabe, K., Broude, E.V., Fang, J., Poole, J.C., Kalinichenko, T.V., and Roninson, I.B. 2000. Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implica- tions for carcinogenesis, senescence, and age-related dis- eases. Proc. Natl. Acad. Sci. 97: 4291-4296.
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Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors
Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · see citing works
Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · see citing works
Self-citationNegative Control of p53 by Sir2α Promotes Cell Survival under Stress
Luo, J., Nikolaev, A. Y., Imai, S.-I., Chen, D., Su, F., Shiloh, A., Guarente, L., & Gu, W. (2001) · Cell · doi:10.1016/s0092-8674(01)00524-4 · Cited by 2,081 · see citing works
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 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
Post-translational modification of p53 in tumorigenesis
Bode, A. M., & Dong, Z. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1455 · Cited by 1,270 · see citing works
Mechanisms and functions of cellular senescence
Herranz, N., & Gil, J. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95148 · Cited by 1,232 · see citing works
Chien, Y., Scuoppo, C., Wang, X., Fang, X., Balgley, B., Bolden, J. E., Premsrirut, P., Luo, W., Chicas, A., Lee, C. S., et al. (2011) · Genes & Development · doi:10.1101/gad.17276711 · Cited by 1,046 · see citing works
Self-citationCellular senescence and its effector programs
Salama, R., Sadaie, M., Hoare, M., & Narita, M. (2014) · Genes & Development · doi:10.1101/gad.235184.113 · Cited by 855 · see citing works
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all
Gil, J., & Peters, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1987 · Cited by 843 · see citing works
Zhang, R., Poustovoitov, M. V., Ye, X., Santos, H. A., Chen, W., Daganzo, S. M., Erzberger, J. P., Serebriiskii, I. G., Canutescu, A. A., Dunbrack, R. L., et al. (2005) · Developmental Cell · doi:10.1016/j.devcel.2004.10.019 · Cited by 699 · see citing works
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654 · see citing works
Self-citationThe dynamic nature of senescence in cancer
Lee, S., & Schmitt, C. A. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0249-2 · Cited by 588 · see citing works
Aging and Genome Maintenance: Lessons from the Mouse?
Hasty, P., Campisi, J., Hoeijmakers, J., van Steeg, H., & Vijg, J. (2003) · Science · doi:10.1126/science.1079161 · Cited by 553 · see citing works
Distinct p53 Transcriptional Programs Dictate Acute DNA-Damage Responses and Tumor Suppression
Brady, C. A., Jiang, D., Mello, S. S., Johnson, T. M., Jarvis, L. A., Kozak, M. M., Broz, D. K., Basak, S., Park, E. J., McLaughlin, M. E., et al. (2011) · Cell · doi:10.1016/j.cell.2011.03.035 · Cited by 533 · see citing works
Vascular Cell Senescence: Contribution to Atherosclerosis
Minamino, T., & Komuro, I. (2007) · Circulation Research · doi:10.1161/01.res.0000256837.40544.4a · Cited by 542 · see citing works
Rodier, F., Muñoz, D. P., Teachenor, R., Chu, V., Le, O., Bhaumik, D., Coppé, J.-P., Campeau, E., Beauséjour, C. M., Kim, S.-H., et al. (2011) · Journal of Cell Science · doi:10.1242/jcs.071340 · Cited by 535 · see citing works
Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence
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Markers of cellular senescence. Telomere shortening as a marker of cellular senescence
Bernadotte, A., Mikhelson, V. M., & Spivak, I. M. (2016) · Aging · doi:10.18632/aging.100871 · Cited by 466 · see citing works
Differentiation therapy revisited
de Thé, H. (2018) · Nature reviews. Cancer · doi:10.1038/nrc.2017.103 · Cited by 462 · see citing works
Molecular dissection of formation of senescence-associated heterochromatin foci
Zhang, R., Chen, W., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02019-06 · Cited by 415 · see citing works
Putting the stress on senescence
Serrano, M., & Blasco, M. A. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00278-7 · Cited by 413 · see citing works
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · see citing works
Self-citationThe DNA damage signaling pathway is a critical mediator of oncogene-induced senescence
Mallette, F. A., Gaumont-Leclerc, M.-F., & Ferbeyre, G. (2007) · Genes & Development · doi:10.1101/gad.1487307 · Cited by 406 · see citing works
Self-citationCellular senescence as a tumor-suppressor mechanism
Campisi, J. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)82148-6 · Cited by 390 · see citing works
Metformin reduces endogenous reactive oxygen species and associated DNA damage
Algire, C., Moiseeva, O., Deschênes-Simard, X., Amrein, L., Petruccelli, L., Birman, E., Viollet, B., Ferbeyre, G., & Pollak, M. N. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-11-0536 · Cited by 372 · see citing works
Self-citationRegulation of cellular senescence by p53
Itahana, K., Dimri, G., & Campisi, J. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02228.x · Cited by 365 · see citing works
Retinoblastoma protein partners
(2001) · Advances in Cancer Research · doi:10.1016/s0065-230x(01)82001-7 · Cited by 349 · see citing works
PML Is a Direct p53 Target that Modulates p53 Effector Functions
de Stanchina, E., Querido, E., Narita, M., Davuluri, R. V., Pandolfi, P. P., Ferbeyre, G., & Lowe, S. W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00062-0 · Cited by 312 · see citing works
Self-citationAstle, M. V., Hannan, K. M., Ng, P. Y., Lee, R. S., George, A. J., Hsu, A. K., Haupt, Y., Hannan, R. D., & Pearson, R. B. (2012) · Oncogene · doi:10.1038/onc.2011.394 · Cited by 295 · see citing works
Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy
Binet, F., Cagnone, G., Crespo-Garcia, S., Hata, M., Neault, M., Dejda, A., Wilson, A. M., Buscarlet, M., Mawambo, G. T., Howard, J. P., et al. (2020) · Science · doi:10.1126/science.aay5356 · Cited by 283 · see citing works
Hubackova, S., Krejcikova, K., Bartek, J., & Hodny, Z. (2012) · Aging · doi:10.18632/aging.100520 · Cited by 272 · see citing works
Oncogene-Induced Senescence: Putting the Brakes on Tumor Development
Braig, M., & Schmitt, C. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4006 · Cited by 274 · see citing works
Cellular senescence and cancer treatment
Schmitt, C. A. (2007) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.08.005 · Cited by 254 · see citing works
DNA Damage Signaling and p53-dependent Senescence after Prolonged β-Interferon Stimulation
Moiseeva, O., Mallette, F. A., Mukhopadhyay, U. K., Moores, A., & Ferbeyre, G. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-09-0858 · Cited by 252 · see citing works
Self-citationRole of p14<sup>ARF</sup> in Replicative and Induced Senescence of Human Fibroblasts
Wei, W., Hemmer, R. M., & Sedivy, J. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.20.6748-6757.2001 · Cited by 217 · see citing works
Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest
Sapieha, P., & Mallette, F. A. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.03.003 · Cited by 193 · see citing works
Deconstructing p53 transcriptional networks in tumor suppression
Bieging, K. T., & Attardi, L. D. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.10.006 · Cited by 194 · see citing works
Tumor suppressor activity of the ERK/MAPK pathway by promoting selective protein degradation
Deschênes-Simard, X., Gaumont-Leclerc, M.-F., Bourdeau, V., Lessard, F., Moiseeva, O., Forest, V., Igelmann, S., Mallette, F. A., Saba-El-Leil, M. K., Meloche, S., et al. (2013) · Genes & Development · doi:10.1101/gad.203984.112 · Cited by 194 · see citing works
Self-citationAssessing cell and organ senescence biomarkers
de Jesus, B. B., & Blasco, M. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.247866 · Cited by 187 · see citing works
Regulation of E2Fs and senescence by PML nuclear bodies
Vernier, M., Bourdeau, V., Gaumont-Leclerc, M.-F., Moiseeva, O., Bégin, V., Saad, F., Mes-Masson, A.-M., & Ferbeyre, G. (2011) · Genes & Development · doi:10.1101/gad.1975111 · Cited by 177 · see citing works
Self-citationMunro, J., Barr, N. I., Ireland, H., Morrison, V., & Parkinson, E. K. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.01.017 · Cited by 141 · see citing works
Biomarkers to identify and isolate senescent cells
Matjusaitis, M., Chin, G., Sarnoski, E. A., & Stolzing, A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.003 · Cited by 144 · see citing works
The DNA Damage Signaling Pathway Connects Oncogenic Stress to Cellular Senescence
Mallette, F. A., & Ferbeyre, G. (2007) · Cell Cycle · doi:10.4161/cc.6.15.4516 · Cited by 125 · see citing works
Self-citation5-Lipoxygenase regulates senescence-like growth arrest by promoting ROS-dependent p53 activation
Catalano, A., Rodilossi, S., Caprari, P., Coppola, V., & Procopio, A. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600502 · Cited by 123 · see citing works
Rowland, B. D., Denissov, S. G., Douma, S., Stunnenberg, H. G., Bernards, R., & Peeper, D. S. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00085-5 · Cited by 120 · see citing works
Huot, T. J., Rowe, J., Harland, M., Drayton, S., Brookes, S., Gooptu, C., Purkis, P., Fried, M., Bataille, V., Hara, E., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.23.8135-8143.2002 · Cited by 107 · see citing works
Replicative senescence revisited.
Marcotte, R., & Wang, E. (2002) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/57.7.b257 · Cited by 86 · see citing works
Regulation of p53 family members by the ubiquitin-like SUMO system
Stehmeier, P., & Muller, S. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.01.002 · Cited by 83 · see citing works
Yates, K. E., Korbel, G. A., Shtutman, M., Roninson, I. B., & DiMaio, D. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00411.x · Cited by 77 · see citing works
Senescence and epigenetic dysregulation in cancer
Neumeister, P., Albanese, C., Balent, B., Greally, J., & Pestell, R. G. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00079-1 · Cited by 56 · see citing works
Old cells, new tricks: chromatin structure in senescence
Parry, A. J., & Narita, M. (2016) · Mammalian Genome · doi:10.1007/s00335-016-9628-9 · Cited by 53 · see citing works
Molecular pathogenesis of acute promyelocytic leukaemia and APL variants
Sirulnik, A., Melnick, A., Zelent, A., & Licht, J. D. (2003) · Best Practice & Research Clinical Haematology · doi:10.1016/s1521-6926(03)00062-8 · Cited by 54 · see citing works
Parisotto, M., Grelet, E., El Bizri, R., Dai, Y., Terzic, J., Eckert, D., Gargowitsch, L., Bornert, J.-M., & Metzger, D. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171207 · Cited by 43 · see citing works
Metabolic alterations accompanying oncogene-induced senescence
Aird, K. M., & Zhang, R. (2014) · Molecular & Cellular Oncology · doi:10.4161/23723548.2014.963481 · Cited by 39 · see citing works
Dulic, V. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-239-1_2 · Cited by 42 · see citing works
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 · see citing works
Münch, S., Weidtkamp-Peters, S., Klement, K., Grigaravicius, P., Monajembashi, S., Salomoni, P., Pandolfi, P. P., Weißhart, K., & Hemmerich, P. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01345-13 · Cited by 32 · see citing works
Overview of molecular signatures of senescence and associated resources: pros and cons
Ntintas, O. A., Vagena, S., Pantelis, P., Theocharous, G., Petty, R., Evangelou, K., & Gorgoulis, V. G. (2026) · FEBS Open Bio · doi:10.1002/2211-5463.70134 · Cited by 6 · see citing works
O-GlcNAcylation of FOXK1 orchestrates the E2F pathway and promotes oncogenesis
Masclef, L., Ahmed, O., Iannantuono, N., Gagnon, J., Gushul-Leclaire, M., Boulay, K., Estavoyer, B., Echbicheb, M., Poy, M., Ali Boubacar, K., et al. (2024) · doi:10.1101/2024.03.01.582838 · Cited by 6 · see citing works
- Authors
- Ferbeyre, G., de Stanchina, E., Querido, E., Baptiste, N., Prives, C., & Lowe, S. W.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Lowe, Scott W.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2000-08-15
- Volume
- 14
- Issue
- 16
- Pages
- 2015-2027
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316863
- OpenAlex
- W2135730738
- Cited by
- 536
- References
- 73
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 13 · 2023: 8 · 2022: 6 · 2021: 15 · 2020: 4 · 2019: 12 · 2018: 12 · 2017: 15 · 2016: 17 · 2015: 16 · 2014: 27 · 2013: 33 · 2012: 25
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- Funders
- Cold Spring Harbor Laboratory
- National Institutes of Health
- National Institute on Aging (R56AG016379, AG-16379, R01AG016379)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- promyelocytic leukemia protein, PML, oncogenic Ras, premature senescence, replicative senescence, p53 phosphorylation, retinoblastoma protein, p16, adenovirus E1A, tumor suppressor, senescence-associated gene expression, IMR-90 fibroblasts
- MeSH terms
- Promyelocytic Leukemia Protein, Humans, Neoplasm Proteins, Nuclear Proteins, Genes, ras, Transcription Factors, Up-Regulation, Tumor Suppressor Protein p53, Retinoblastoma Protein, Cellular Senescence, Tumor Suppressor Proteins
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