Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?

Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?
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DOI:
10.1038/nrc2960
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发表时间:
2010-12
期刊:
Nature reviews. Cancer
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其他
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现在有大量且不断增加的证据表明,小GTP酶的Ras超家族的异常活性在人类癌症中起因果作用。这些GTP酶作为GDP - GTP调节的二元开关,控制着许多基本的细胞过程。癌症中GTP酶失调的一个常见机制是其调节蛋白——促进形成活性GTP结合状态的鸟嘌呤核苷酸交换因子(GEFs)和使GTP酶恢复到其GDP结合的非活性状态的GTP酶激活蛋白(GAPs)的表达和/或活性失调。我们评估了GEFs和GAPs与癌症的关联以及它们在癌症治疗中的成药性。
There is now considerable and increasing evidence for a causal role of aberrant activity of the Ras superfamily of small GTPases in human cancers. These GTPases act as GDP-GTP-regulated binary switches that control many fundamental cellular processes. A common mechanism of GTPase deregulation in cancer is the deregulated expression and/or activity of their regulatory proteins, guanine nucleotide exchange factors (GEFs) that promote formation of the active GTP-bound state and GTPase activating proteins (GAPs) that return the GTPase to its GDP-bound inactive state. We assess the association of GEFs and GAPs with cancer and their druggability for cancer therapeutics.
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