泛素连接酶Siah2与缺氧反应
The ubiquitin ligase Siah2 and the hypoxia response.
作者信息
Nakayama Koh, Qi Jianfei, Ronai Ze'ev
机构信息
Burnham Institute for Medical Research, La Jolla, CA, USA.
出版信息
Mol Cancer Res. 2009 Apr;7(4):443-51. doi: 10.1158/1541-7786.MCR-08-0458.
Abstract
Growing evidence indicates that ubiquitin ligases play a critical role in the hypoxia response. Among them, Siah2, a RING finger ligase, is an important regulator of pathways activated under hypoxia. Siah2 regulates prolyl hydroxylases PHD3 and 1 under oxygen concentration of 2% to 5%, thereby allowing accumulation of hypoxia-inducible factor (HIF)-1alpha, a master regulator of the hypoxia response within the range of physiological normoxic to mild hypoxic conditions. Growing evidence also indicates an important function for Siah2 in tumor development and progression based on pancreatic cancer, mammary tumor, and melanoma mouse models. This review summarizes our current understanding of Siah2 regulation and function with emphasis on hypoxia and tumorigenesis.
摘要
越来越多的证据表明，泛素连接酶在缺氧反应中起关键作用。其中，RING指状结构连接酶Siah2是缺氧时激活的信号通路的重要调节因子。在2%至5%的氧浓度下，Siah2调节脯氨酰羟化酶PHD3和PHD1，从而使缺氧诱导因子（HIF）-1α积累，HIF-1α是生理常氧至轻度缺氧条件范围内缺氧反应的主要调节因子。基于胰腺癌、乳腺肿瘤和黑色素瘤小鼠模型的越来越多的证据也表明Siah2在肿瘤发生和发展中具有重要作用。本综述总结了我们目前对Siah2调节和功能的理解，重点是缺氧和肿瘤发生。
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The ubiquitin ligase Siah2 regulates tumorigenesis and metastasis by HIF-dependent and -independent pathways.泛素连接酶Siah2通过HIF依赖和非依赖途径调节肿瘤发生和转移。
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