Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance
Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance
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DOI：
10.1038/ncb1258
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发表时间：
2005-06-01
影响因子：
21.3
通讯作者：
Blenis, J
中科院分区：
文献类型：
--
作者：
MacKeigan, JP;Murphy, LO;Blenis, J
逃避细胞凋亡是癌症的一个标志，最近利用靶向治疗的成功强调了识别抗细胞凋亡生存途径的重要性。在这里，我们利用RNA干扰(RNAi)系统地筛选人类基因组中的激酶和磷酸酶组分。除了已知的激酶外，我们还发现了几种新的生存激酶。有趣的是，许多磷酸酶和相关的调节亚基有助于细胞存活，揭示了以前未被认识的磷酸酶作为细胞凋亡负调节因子的一般作用。我们还鉴定了具有肿瘤抑制物样活性的一组磷酸酶。最后，以特定蛋白激酶为靶点的RNAi使耐药细胞对化疗药物敏感。针对这些激酶或磷酸酶的抑制剂的开发可能会导致新的抗癌策略。
Evasion from apoptosis is a hallmark of cancer, and recent success using targeted therapeutics underscores the importance of identifying anti-apoptotic survival pathways. Here we utilize RNA interference (RNAi) to systematically screen the kinase and phosphatase component of the human genome. In addition to known kinases, we identified several new survival kinases. Interestingly, numerous phosphatases and associated regulatory subunits contribute to cell survival, revealing a previously unrecognized general role for phosphatases as negative regulators of apoptosis. We also identified a subset of phosphatases with tumour-suppressor-like activity. Finally, RNAi targeting of specific protein kinases sensitizes resistant cells to chemotherapeutic agents. The development of inhibitors that target these kinases or phosphatases may lead to new anti-cancer strategies.