Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence
Abstract
The p16INK4a cyclin-dependent kinase inhibitor is implicated in replicative senescence, the state of permanent growth arrest provoked by cumulative cell divisions or as a response to constitutive Ras-Raf-MEK signalling in somatic cells. Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor but the mechanisms regulating its expression in these different contexts remain unknown. Here we demonstrate a role for the Ets1 and Ets2 transcription factors based on their ability to activate the p16INK4a promoter through an ETS-binding site and their patterns of expression during the lifespan of human diploid fibroblasts. The induction of p16INK4a by Ets2, which is abundant in young human diploid fibroblasts, is potentiated by signalling through the Ras-Raf-MEK kinase cascade and inhibited by a direct interaction with the helix-loop-helix protein Id1 (ref. 11). In senescent cells, where the Ets2 levels and MEK signalling decline, the marked increase in p16INK4a expression is consistent with the reciprocal reduction of Id1 and accumulation of Ets1.
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Expression of Ets-1, a transcriptional activator of p16, correlated with p16 expression, although absolute levels of Ets-1 did not necessarily increase with age.
“In addition, expression of Ets-1, a transcriptional activator of p16 (Ohtani et al., 2001), correlated with p16 expression, although absolute levels of Ets-1 did not necessarily increase with age (Krishnamurthy et al., 2004).”
From Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors (2005) · cites this paper as Ohtani et al., 2001
Oncogene activation can upregulate p16 expression through the transcription factors Ets-1 and -2.
“Oncogene activation can upregulate p16 expression through the transcription factors Ets-1 and -2 [17].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [17]
These precancerous cells show phenotypes of cellular senescence through DNA replication stress and MAPK-mediated activation of p16 transcription.
“These cells show phenotypes of cellular senescence [35] through DNA replication stress [36] and mitogen-activated protein kinase (MAPK)-mediated activation of p16 transcription [17].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [17]
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
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
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
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750 · 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 · see citing works
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Serrano, M., Hannon, G. J., & Beach, D. (1993) · Nature · doi:10.1038/366704a0 · Cited by 3,650 · see citing works
The protein Id: A negative regulator of helix-loop-helix DNA binding proteins
Benezra, R., Davis, R. L., Lockshon, D., Turner, D. L., & Weintraub, H. M. (1990) · Cell · doi:10.1016/0092-8674(90)90214-y · Cited by 2,202 · see citing works
Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms
Massari, M. E., & Murre, C. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.2.429-440.2000 · Cited by 1,800 · see citing works
Jacobs, J. J. L., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999) · Nature · doi:10.1038/16476 · Cited by 1,580 · see citing works
Alcorta, D. A., Xiong, Y., Phelps, D., Hannon, G., Beach, D., & Barrett, J. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13742 · Cited by 1,008 · 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
Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts
Lyden, D. C., Young, A. Z., Zagzag, D., Yan, W. X., Gerald, W. L., O'Reilly, R., Bader, B., Hynes, R. O., Zhuang, Y., Manova, K., et al. (1999) · Nature · doi:10.1038/44334 · Cited by 912 · see citing works
The p16INK4a/CDKN2A tumor suppressor and its relatives
Ruas, M., & Peters, G. (1998) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(98)00017-1 · Cited by 911 · 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
Hara, E., Smith, R., Parry, D., Tahara, H., Stone, S., & Peters, G. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.859 · Cited by 733 · see citing works
Self-citationTakahashi, Y., Rayman, J. B., & Dynlacht, B. D. (2000) · Genes & Development · doi:10.1101/gad.14.7.804 · Cited by 621 · see citing works
Specificity within the ets Family of Transcription Factors
(1998) · Advances in Cancer Research · doi:10.1016/s0065-230x(08)60738-1 · Cited by 344 · 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
Self-citationGenes involved in senescence and immortalization
Lundberg, A. S., Hahn, W. C., Gupta, P., & Weinberg, R. A. (2000) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00155-1 · Cited by 313 · see citing works
Hara, E., Yamaguchi, T., Nojima, H., Ide, T., Campisi, J., Okayama, H., & Oda, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42146-6 · Cited by 311 · see citing works
Self-citationSedivy, J. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9078 · Cited by 182 · see citing works
(1996) · PubMed · Cited by 180 · see citing works
Yates, P. R., Atherton, G. T., Deed, R. W., Norton, J. D., & Sharrocks, A. D. (1999) · The EMBO Journal · doi:10.1093/emboj/18.4.968 · Cited by 152 · see citing works
Self-citationLoughran, Ö., Malliri, A., Owens, D., Gallimore, P. H., Stanley, M., Ozanne, B. W., Frame, M. C., & Parkinson, E. K. (1996) · PubMed · Cited by 143 · see citing works
Immortalization of primary human keratinocytes by the helix–loop–helix protein, Id-1
Alani, R. M., Hasskarl, J., Grace, M. R., Hernandez, M.-C., Israel, M. A., & Münger, K. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9637 · Cited by 137 · see citing works
Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1Preprint
Sugimoto, M., Nakamura, T., Ohtani, N., Hampson, L., HAMPSON, I. N., Shimamoto, A., Furuichi, Y., Okumura, K., Niwa, S., Taya, Y., et al. (1999) · Genes & Development · doi:10.1101/gad.13.22.3027 · Cited by 105 · see citing works
Self-citationFoos, G. E., Garcı́a-Ramı́rez, J. J., Galang, C. K., & Hauser, C. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.30.18871 · Cited by 51 · see citing works
Telomerase activity in human germline and embryonic tissues and cells
Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W., & Shay, J. W. (1996) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1996)18:2
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Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441 · see citing works
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
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
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926 · see citing works
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Herbig, U., Jobling, W. A., Chen, B. P. C., Chen, D. J., & Sedivy, J. M. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00256-4 · Cited by 1,344 · see citing works
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270 · see citing works
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284 · see citing works
Oncogene-induced senescence as an initial barrier in lymphoma development
Braig, M., Lee, S., Loddenkemper, C., Rudolph, C., Peters, A. H. F. M., Schlegelberger, B., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2005) · Nature · doi:10.1038/nature03841 · Cited by 1,220 · see citing works
The ETS-domain transcription factor family
Sharrocks, A. D. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35099076 · Cited by 1,086 · see citing works
Self-citationChien, 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
Aguirre, A. J., Bardeesy, N., Sinha, M., Lopez, L., Tuveson, D. A., Horner, J., Redston, M. S., & DePinho, R. A. (2003) · Genes & Development · doi:10.1101/gad.1158703 · Cited by 1,033 · see citing works
The Regulation of INK4/ARF in Cancer and Aging
Kim, W. Y., & Sharpless, N. E. (2006) · Cell · doi:10.1016/j.cell.2006.10.003 · Cited by 1,009 · see citing works
Cellular senescence and tumor suppressor gene p16
Rayess, H., Wang, M. B., & Srivatsan, E. S. (2012) · International Journal of Cancer · doi:10.1002/ijc.27316 · Cited by 825 · 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
Self-citationExosomes maintain cellular homeostasis by excreting harmful DNA from cells
Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M. T., Obuse, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms15287 · Cited by 761 · see citing works
Self-citationTumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · see citing works
The 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
Id proteins in development, cell cycle and cancer
Ruzinova, M. B., & Benezra, R. (2003) · Trends in Cell Biology · doi:10.1016/s0962-8924(03)00147-8 · Cited by 570 · see citing works
p16 <sup>INK4A</sup> is a robust <i>in vivo</i> biomarker of cellular aging in human skin
Ressler, S., Bartkova, J., Niederegger, H., Bartek, J., Scharffetter‐Kochanek, K., Jansen‐Dürr, P., & Wlaschek, M. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00231.x · Cited by 557 · 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
Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S.-I., Tahara, H., Nakayama, K., Nakayama, K. I., Ide, T., Saya, H., & Hara, E. (2006) · Nature Cell Biology · doi:10.1038/ncb1491 · Cited by 528 · see citing works
Self-citationCellular senescence in brain aging and neurodegenerative diseases: evidence and perspectives
Baker, D. J., & Petersen, R. C. (2018) · Journal of Clinical Investigation · doi:10.1172/jci95145 · Cited by 514 · see citing works
A negative feedback signaling network underlies oncogene-induced senescence
Courtois-Cox, S., Genther Williams, S. M., Reczek, E. E., Johnson, B. W., McGillicuddy, L. T., Johannessen, C. M., Hollstein, P. E., MacCollin, M., & Cichowski, K. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.003 · Cited by 501 · see citing works
Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1
Itahana, K., Zou, Y., Itahana, Y., Martinez, J.-L., Beausejour, C., Jacobs, J. J. L., van Lohuizen, M., Band, V., Campisi, J., & Dimri, G. P. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.1.389-401.2003 · Cited by 438 · 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
Cellular 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
p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC
Christoffersen, N. R., Shalgi, R., Frankel, L. B., Leucci, E., Lees, M., Klausen, M., Pilpel, Y., Nielsen, F. C., Oren, M., & Lund, A. H. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.109 · Cited by 352 · see citing works
Mechanisms of cellular senescence in human and mouse cells.
Itahana, K., Campisi, J., & Dimri, G. P. (2004) · Biogerontology · doi:10.1023/b:bgen.0000017682.96395.10 · Cited by 338 · see citing works
Rheinwald, J. G., Hahn, W. C., Ramsey, M. R., Wu, J. Y., Guo, Z., Tsao, H., De Luca, M., Catricalà, C., & O'Toole, K. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.14.5157-5172.2002 · Cited by 338 · see citing works
Retinoic acid signaling and neuronal differentiation
Janesick, A., Wu, S. C., & Blumberg, B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1815-9 · Cited by 295 · see citing works
Ohtani, N., Yamakoshi, K., Takahashi, A., & Hara, E. (2004) · The Journal of Medical Investigation · doi:10.2152/jmi.51.146 · Cited by 276 · see citing works
Self-citationp16INK4a Translation Suppressed by miR-24
Lal, A., Kim, H. H., Abdelmohsen, K., Kuwano, Y., Pullmann, R., Srikantan, S., Subrahmanyam, R., Martindale, J. L., Yang, X., Ahmed, F., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001864 · Cited by 268 · see citing works
“was shown to be induced by transcription factors such as Ets1, Ets2, and JunB [12,13] and repressed by transcription factors such as Id1 and Id3 [13,14] and by Bmi-1 [15].”
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
Loo, T. M., Miyata, K., Tanaka, Y., & Takahashi, A. (2020) · Cancer Science · doi:10.1111/cas.14266 · Cited by 232 · see citing works
The Id proteins and angiogenesis
Benezra, R., Rafii, S., & Lyden, D. (2001) · Oncogene · doi:10.1038/sj.onc.1205160 · Cited by 222 · see citing works
Role 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
Herdy, J. R., Traxler, L., Agarwal, R. K., Karbacher, L., Schlachetzki, J. C. M., Boehnke, L., Zangwill, D., Galasko, D., Glass, C. K., Mertens, J., et al. (2022) · Cell Stem Cell · doi:10.1016/j.stem.2022.11.010 · Cited by 208 · see citing works
Epigenetic regulation of the<i>INK4b-ARF-INK4a</i>locus: In sickness and in health
Popov, N., & Gil, J. (2010) · Epigenetics · doi:10.4161/epi.5.8.12996 · Cited by 202 · see citing works
Gentile, M. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg675 · Cited by 185 · see citing works
Lessard, F., Igelmann, S., Trahan, C., Huot, G., Saint-Germain, E., Mignacca, L., Del Toro, N., Lopes-Paciencia, S., Le Calvé, B., Montero, M., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0127-y · Cited by 174 · see citing works
Real-time in vivo imaging of p16Ink4a reveals cross talk with p53
Yamakoshi, K., Takahashi, A., Hirota, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D. J., Ohmura, M., Hirao, A., Saya, H., et al. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200904105 · Cited by 172 · see citing works
Self-citationThe role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144 · 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
Ink4a/Arf links senescence and aging
Sharpless, N. E. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.06.025 · Cited by 142 · see citing works
Site-specific DNA methylation by a complex of PU.1 and Dnmt3a/b
Suzuki, M., Yamada, T., Kihara-Negishi, F., Sakurai, T., Hara, E., Tenen, D. G., Hozumi, N., & Oikawa, T. (2006) · Oncogene · doi:10.1038/sj.onc.1209272 · Cited by 132 · see citing works
Self-citationChkhotua, A. B., Gabusi, E., Altimari, A., D’Errico, A., Yakubovich, M., Vienken, J., Stefoni, S., Chieco, P., Yussim, A., & Grigioni, W. F. (2003) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(03)00363-9 · Cited by 120 · see citing works
Paramos-de-Carvalho, D., Jacinto, A., & Saúde, L. (2021) · eLife · doi:10.7554/elife.72449 · Cited by 111 · see citing works
Xu, P., Wang, M., Song, W.-M., Wang, Q., Yuan, G.-C., Sudmant, P. H., Zare, H., Tu, Z., Orr, M. E., & Zhang, B. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00507-7 · Cited by 114 · 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
Self-citationTranscriptional regulation of cellular senescence
Lanigan, F., Geraghty, J. G., & Bracken, A. P. (2011) · Oncogene · doi:10.1038/onc.2011.34 · Cited by 95 · see citing works
Park, H., Kim, C.-H., Jeong, J.-H., Park, M., & Kim, K. S. (2016) · Oncotarget · doi:10.18632/oncotarget.7457 · Cited by 92 · 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
PPARγ accelerates cellular senescence by inducing p16INK4α expression in human diploid fibroblasts
Gan, Q., Huang, J., Zhou, R., Niu, J., Zhu, X., Wang, J., Zhang, Z., & Tong, T. (2008) · Journal of Cell Science · doi:10.1242/jcs.026633 · Cited by 82 · see citing works
Hematopoietic stem cell ageing is uncoupled from p16INK4A-mediated senescence
Attema, J. L., Pronk, C. J. H., Norddahl, G. L., Nygren, J. M., & Bryder, D. (2009) · Oncogene · doi:10.1038/onc.2009.94 · Cited by 72 · see citing works
Sasaki, M., Kajiya, H., Ozeki, S., Okabe, K., & Ikebe, T. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.123 · Cited by 67 · see citing works
Elsallabi, O., Patruno, A., Pesce, M., Cataldi, A., Carradori, S., & Gallorini, M. (2022) · Molecules · doi:10.3390/molecules27030738 · Cited by 67 · see citing works
Wang, W., Wu, J., Zhang, Z., & Tong, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108278200 · Cited by 66 · see citing works
Evangelou, 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 · see citing works
Proliferative arrest and cell cycle regulation in CD8+CD28− versus CD8+CD28+ T cells
Scheuring, U. J., Sabzevari, H., & Theofilopoulos, A. N. (2002) · Human Immunology · doi:10.1016/s0198-8859(02)00683-3 · Cited by 59 · see citing works
Cellular senescence: a double‐edged sword in the fight against cancer
Ohtani, N., Takahashi, A., Mann, D. J., & Hara, E. (2012) · Experimental Dermatology · doi:10.1111/j.1600-0625.2012.01493.x · Cited by 57 · see citing works
Self-citationSenescence 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
Berent-Maoz, B., Montecino-Rodriguez, E., Signer, R. A. J., & Dorshkind, K. (2012) · Blood · doi:10.1182/blood-2011-12-400002 · Cited by 46 · see citing works
Straume, O., & Akslen, L. A. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602792 · Cited by 42 · see citing works
Stress-induced cellular senescence contributes to chronic inflammation and cancer progression.
KOBASHIGAWA, S., M. SAKAGUCHI, Y., MASUNAGA, S., & MORI, E. (2019) · Thermal Medicine · doi:10.3191/thermalmed.35.41 · Cited by 18 · see citing works
- Authors
- Ohtani, N., Zebedee, Z., Huot, T. J. G., Stinson, J. A., Sugimoto, M., Ohashi, Y., Sharrocks, A. D., Peters, G., & Hara, E.
- Affiliations
- Cancer Research UK Manchester Institute (GB)
- University of Manchester (GB)
- Juntendo University (JP)
- Corresponding author
- Hara, Eiji
- Venue
- Nature
- Published
- 2001-02
- Volume
- 409
- Issue
- 6823
- Pages
- 1067-1070
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2035532250
- Cited by
- 654
- References
- 28
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 13 · 2023: 9 · 2022: 24 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 15 · 2017: 18 · 2016: 17 · 2015: 20 · 2014: 21 · 2013: 27 · 2012: 20
- FWCI
- 29.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy
- Wellcome Trust
- Institute of Molecular and Cell Biology
- 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
- p16INK4a, cellular senescence, replicative senescence, ETS1, ETS2, Id1, helix-loop-helix proteins, transcriptional regulation, Ets binding site, human diploid fibroblasts, tumour suppressor, growth arrest
- MeSH terms
- Animals, Cell Line, DNA-Binding Proteins, Fibroblasts, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Trans-Activators, Cellular Senescence, Protein Serine-Threonine Kinases, ras Proteins, Proto-Oncogene Proteins c-raf, Cyclin-Dependent Kinase Inhibitor p16, MAP Kinase Signaling System, MAP Kinase Kinase Kinase 1, Proto-Oncogene Proteins c-ets, Proto-Oncogene Protein c-ets-1, Proto-Oncogene Protein c-ets-2, Mice, Inhibitor of Differentiation Protein 1
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 ›
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