Hypoxia, HIFs, and cardiovascular development.
Hypoxia, HIFs, and cardiovascular development.
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缺氧、HIF 和心血管发育。
DOI：
10.1101/sqb.2002.67.127
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Mansfield,K
中科院分区：
文献类型：
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作者：
Simon,MC;Ramirez-Bergeron,D;Mack,F;Hu,CJ;Pan,Y;Mansfield,K
《冷泉港定量生物学研讨会》，卷LXVII，© 2002冷泉港实验室出版社0-87969-678-8/02。127表明缺氧通过涉及增加的反应性O2物质（ROS）的依赖性信号传导过程激活HIF（Chandel等，1998，2000）。最近的实验表明，脯氨酰羟化酶修饰HIF-1α、HIF-2α和HIF-3α的O2依赖性降解结构域（ODD）内脯氨酸残基上的HIFα亚基（Ivan et al. 2001; Jaakkola et al. 2001; Yu et al. 2001）。虽然脯氨酰羟化ODD是必要的，足以使HIFα结合pVHL，导致随后的泛素化，它仍然是一个正式的可能性，ROS的脯氨酰羟化酶酶活性的上游行动。我们目前正在研究一种模型，即在常氧培养条件下，线粒体功能对所有HIFα亚基上的脯氨酰羟基化至关重要。
Cold Spring Harbor Symposia on Quantitative Biology, Volume LXVII.© 2002 Cold Spring Harbor Laboratory Press 0-87969-678-8/02. 127 cates that hypoxia activates HIF via a mitochondriadependent signaling process involving increased reactive O2 species (ROS)(Chandel et al. 1998, 2000). More recent experiments have shown that prolyl hydroxylases modify HIFα subunits on proline residues within the O2-dependent degradation domain (ODD) of HIF-1α, HIF-2α, and HIF-3α (Ivan et al. 2001; Jaakkola et al. 2001; Yu et al. 2001). Although prolyl hydroxylation of the ODDs is necessary and sufficient to allow HIFα to bind pVHL, causing subsequent ubiquination, it remains a formal possibility that ROS act upstream of prolyl hydroxylase enzymatic activity. We are currently investigating a model whereby mitochondrial function is essential for prolyl hydroxylation on all HIFα subunits during normoxic culture conditions.