COP1是一种瘤抑制剂,导致ETS转录因子的降解
Alberto C Vitari1, Kevin G Leong, Kim Newton
1Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|May 17, 2011
概括
无素酶COP1 (也称为RFWD2) 通过降解ETV1,ETV4和ETV5.5起到瘤抑制作用. 它的损失促进前列腺癌的发展和侵袭性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 原型瘤基因ETV1,ETV4和ETV5在前列腺癌中经常发生变化.
- 它们的翻译后调节对于发展至关重要,人们对其了解甚少.
研究的目的:
- 确定ETV1,ETV4和ETV5.5的监管机构.
- 研究COP1在前列腺癌中的作用.
主要方法:
- 在COP1.0之前进行Ubiquitination测试以评估ETV1降解.
- 对COP1结合动机的前列腺癌转位的分析 (TMPRSS2:ETV1).
- 在小鼠模型中,前列腺特异性COP1缺陷.
- 对人类前列腺癌样本进行COP1和ETV1变化的分析.
主要成果:
- COP1 无处不在并降解ETV1,ETV4 和ETV5.
- 前列腺癌转位会产生COP1不敏感的ETV1变体.
- 在小鼠中,COP1缺乏会增加ETV1水平,导致增生和前新生病变.
- 失去COP1和PTEN会增加前列腺腺癌的侵袭性.
- 人类前列腺癌显示COP1损失和升高的ETV1.
结论:
- COP1是一种瘤抑制剂,可以负面调节ETV1,ETV4和ETV5.
- COP1下调促进前列腺上皮细胞的增殖和瘤发生.
- 通过转位或基因丢失的COP1无活化,在前列腺癌的发展中具有选择性优势.
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