The ubiquitin ligase Siah2 and the hypoxia response.
The ubiquitin ligase Siah2 and the hypoxia response.
复制标题
DOI：
10.1158/1541-7786.mcr-08-0458
复制
发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Ronai Z
中科院分区：
文献类型：
--
作者：
Nakayama K;Qi J;Ronai Z
越来越多的证据表明，泛素连接酶在缺氧反应中起着至关重要的作用。其中，Siah 2是一种环指连接酶，是缺氧条件下激活的重要调节剂。Siah 2在2%至5%的氧浓度下调节脯氨酰羟化酶PHD 3和PHD 1，从而允许缺氧诱导因子（HIF）-1α的积累，HIF-1 α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。越来越多的证据也表明Siah 2在基于胰腺癌、乳腺肿瘤和黑色素瘤小鼠模型的肿瘤发展和进展中的重要功能。本文综述了我们目前对Siah 2调节和功能的理解，重点是缺氧和肿瘤发生。
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)-1α, 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.