Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence

Naoko Ohtani, Zoe Zebedee, Thomas J. G. Huot, Julie A. Stinson, Masataka Sugimoto, Yasuhiro Ohashi, Andrew D. Sharrocks, Gordon Peters and Eiji Hara ()
Additional contact information
Naoko Ohtani: CRC Cell Cycle Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust
Zoe Zebedee: CRC Cell Cycle Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust
Thomas J. G. Huot: Imperial Cancer Research Fund Laboratories
Julie A. Stinson: School of Biological Sciences, University of Manchester
Masataka Sugimoto: CRC Cell Cycle Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust
Yasuhiro Ohashi: Laboratory of Molecular Biology, Nihon Schering K.K.
Andrew D. Sharrocks: School of Biological Sciences, University of Manchester
Gordon Peters: Imperial Cancer Research Fund Laboratories
Eiji Hara: CRC Cell Cycle Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust

Nature, 2001, vol. 409, issue 6823, 1067-1070

Abstract: Abstract The p16INK4a cyclin-dependent kinase inhibitor1 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 cells2,3,4,5,6,7,8. Some contribution to senescence presumably underlies the importance of p16INK4a as a tumour suppressor9 but the mechanisms regulating its expression in these different contexts remain unknown. Here we demonstrate a role for the Ets1 and Ets2 transcription factors10 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.

Date: 2001
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/35059131 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:409:y:2001:i:6823:d:10.1038_35059131

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35059131

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().