Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence.
Authors
Ohtani, NaokoZebedee, Zoe
Huot, Thomas J G
Stinson, Julie A
Sugimoto, Masataka
Ohashi, Yasuhiro
Sharrocks, Andrew D
Peters, Gordon
Hara, Eiji
Affiliation
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.Issue Date
2001-02-22
Metadata
Show full item recordAbstract
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.Citation
Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence. 2001, 409 (6823):1067-70 NatureJournal
NatureDOI
10.1038/35059131PubMed ID
11234019Type
ArticleLanguage
enISSN
0028-0836ae974a485f413a2113503eed53cd6c53
10.1038/35059131
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