Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS

被引：291

作者：

Barradas, Marta ^{[2
]}

Anderton, Emma ^{[1
]}

Acosta, Juan Carlos ^{[2
]}

Li, SiDe ^{[3
,4
]}

Banito, Ana ^{[2
]}

Rodriguez-Niedenfuehr, Marc ^{[1
]}

Maertens, Goedele ^{[1
]}

Banck, Michaela ^{[5
]}

Zhou, Ming-Ming ^{[4
]}

Walsh, Martin J. ^{[3
,4
]}

Peters, Gordon ^{[1
]}

Gil, Jesus ^{[2
]}

机构：

[1] CRUK London Res Inst, Mol Oncol Lab, London WC2A 3PX, England

[2] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, Cell Proliferat Grp, London W12 0NN, England

[3] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA

[5] Mt Sinai Sch Med, Div Hematol & Oncol, Dept Med, New York, NY 10029 USA

来源：

GENES & DEVELOPMENT | 2009年 / 23卷 / 10期

关键词：

Polycomb; senescence; histone methylation; INK4a; JmjC proteins; TUMOR-SUPPRESSOR LOCUS; CELLULAR SENESCENCE; H3K27; DEMETHYLASE; P16(INK4A); CANCER; CELLS; H3; MELANOMA; P19(ARF); DIFFERENTIATION;

D O I：

10.1101/gad.511109

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The INK4a/ARF tumor suppressor locus, a key executor of cellular senescence, is regulated by members of the Polycomb group (PcG) of transcriptional repressors. Here we show that signaling from oncogenic RAS overrides PcG-mediated repression of INK4a by activating the H3K27 demethylase JMJD3 and down-regulating the methyltransferase EZH2. In human fibroblasts, JMJD3 activates INK4a, but not ARF, and causes p16(INK4a)-dependent arrest. In mouse embryo fibroblasts, Jmjd3 activates both Ink4a and Arf and elicits a p53-dependent arrest, echoing the effects of RAS in this system. Our findings directly implicate JMJD3 in the regulation of INK4a/ARF during oncogene-induced senescence and suggest that JMJD3 has the capacity to act as a tumor suppressor.

引用

页码：1177 / 1182

页数：6

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