ZRF1 controls oncogene-induced senescence through the INK4-ARF locus

J. D. Ribeiro, LLuis Morey, A. Mas, A. Gutierrez, N. M. Luis, S. Mejetta, H. Richly, S. A. Benitah, W. M. Keyes, L. Di Croce

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The reactivation of the INK4-ARF locus, which is epigenetically repressed by Polycomb proteins in healthy cells, is a hallmark of senescence. One mechanism of reactivating Polycomb-silenced genes is mediated by the epigenetic factor ZRF1, which associates with ubiquitinated histone H2A. We show that cells undergoing senescence following oncogenic Ras expression have increased ZRF1 levels, and that this binds to the p15INK4b, ARF and p16INK4a promoters. Furthermore, ZRF1 depletion in oncogenic Ras-expressing cells restores proliferation by preventing Arf and p16Ink4a expression, consequently bypassing senescence. Thus, ZRF1 regulates the INK4-ARF locus during cellular proliferation and senescence, and alterations in ZRF1 may contribute to tumorigenesis.

Original languageEnglish (US)
Pages (from-to)2161-2168
Number of pages8
JournalOncogene
Volume32
Issue number17
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Cell Aging
Oncogenes
Cell Proliferation
Epigenomics
Histones
Carcinogenesis
Genes
Proteins
chromatin conjugate protein A24

Keywords

  • chromatin
  • Polycomb
  • senescence
  • ZRF1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ribeiro, J. D., Morey, LL., Mas, A., Gutierrez, A., Luis, N. M., Mejetta, S., ... Di Croce, L. (2013). ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. Oncogene, 32(17), 2161-2168. https://doi.org/10.1038/onc.2012.241

ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. / Ribeiro, J. D.; Morey, LLuis; Mas, A.; Gutierrez, A.; Luis, N. M.; Mejetta, S.; Richly, H.; Benitah, S. A.; Keyes, W. M.; Di Croce, L.

In: Oncogene, Vol. 32, No. 17, 01.01.2013, p. 2161-2168.

Research output: Contribution to journalArticle

Ribeiro, JD, Morey, LL, Mas, A, Gutierrez, A, Luis, NM, Mejetta, S, Richly, H, Benitah, SA, Keyes, WM & Di Croce, L 2013, 'ZRF1 controls oncogene-induced senescence through the INK4-ARF locus', Oncogene, vol. 32, no. 17, pp. 2161-2168. https://doi.org/10.1038/onc.2012.241
Ribeiro JD, Morey LL, Mas A, Gutierrez A, Luis NM, Mejetta S et al. ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. Oncogene. 2013 Jan 1;32(17):2161-2168. https://doi.org/10.1038/onc.2012.241
Ribeiro, J. D. ; Morey, LLuis ; Mas, A. ; Gutierrez, A. ; Luis, N. M. ; Mejetta, S. ; Richly, H. ; Benitah, S. A. ; Keyes, W. M. ; Di Croce, L. / ZRF1 controls oncogene-induced senescence through the INK4-ARF locus. In: Oncogene. 2013 ; Vol. 32, No. 17. pp. 2161-2168.
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