A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20.
A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20.
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除了等位基因突变外，众所周知，癌症的染色质图谱也存在变化。在这里，我们表明，基因组切割SMurf2，一个Hect结构域的E3泛素连接酶，导致DNA损伤反应和基因组稳定性的失调，最终增加老年小鼠对各种类型癌症的易感性。我们证明，SMurf2通过靶向RNF20在小鼠和人类细胞中对蛋白酶体的降解来调节组蛋白H2 B的单泛素化以及组蛋白H3在K4和K79的三甲基化。我们进一步证明，SMurf2和RNF20共定位于细胞核双链断裂的γ-H_2AX焦点。因此，SMurf2具有肿瘤抑制功能，通常通过RNF20控制组蛋白修饰的表观遗传格局来维持基因组的稳定性。
In addition to allelic mutations, cancers are known to harbor alterations in their chromatin landscape. Here, we show that genomic ablation of Smurf2, a HECT-domain E3 ubiquitin ligase, results in dysregulation of DNA damage response and genomic stability, culminating 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 to proteasomal degradation in both mouse and human cells. We further show that Smurf2 and RNF20 are co-localized at the γ-H2AX foci of double-stranded DNA breaks in the nucleus. Thus, Smurf2 has a tumor suppression function that normally maintains genomic stability by controlling the epigenetic landscape of histone modifications through RNF20.
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DOI：
10.1038/nrg2881
发表时间：
2010-11
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1083/jcb.200704140
发表时间：
2007-09-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Murga M;Jaco I;Fan Y;Soria R;Martinez-Pastor B;Cuadrado M;Yang SM;Blasco MA;Skoultchi AI;Fernandez-Capetillo O
通讯作者：
Fernandez-Capetillo O
影响因子：
8
作者：
Li, HX;Seth, A
通讯作者：
Seth, A
影响因子：
16
作者：
Moyal L;Lerenthal Y;Gana-Weisz M;Mass G;So S;Wang SY;Eppink B;Chung YM;Shalev G;Shema E;Shkedy D;Smorodinsky NI;van Vliet N;Kuster B;Mann M;Ciechanover A;Dahm-Daphi J;Kanaar R;Hu MC;Chen DJ;Oren M;Shiloh Y
通讯作者：
Shiloh Y
影响因子：
16
作者：
Kavsak, P;Rasmussen, RK;Wrana, JL
通讯作者：
Wrana, JL