A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-3

Authors

• M Blank
• Y Tang
• M Yamashita
• SS Burkett
• SY Cheng
• YE Zhang

Abstract

Cancers are known to harbour alterations in chromatin landscape in addition to allelic mutations. Here, we show that genomic ablation of Smurf2, a HECT-domain E3 ubiquitin ligase, results in deregulation of global gene expression, altered DNA damage response, and unstable genomes, which culminate to increased susceptibility to various types of cancers in aged mice. We demonstrate that Smurf2 regulates histone H2B monoubiquitination as well as histone H3 tri-methylation at K4 and K79 by targeting RNF20, the major E3 ligase for histone H2B ubiquitination, to proteasomal degradation. We further show that Smurf2 and RNF20 are co-localized at the g-H2AX foci of double strand DNA breaks in the nucleus, and Smurf2 regulates RNF20 stability in human cancer cells. Thus, our data indicate that Smurf2 has a tumor suppression function that normally maintains genome stability by controlling the epigenetic landscape of histone modifications through RNF20.

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