Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations
Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations
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DOI：
10.1073/pnas.080072497
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Semenza, GL
中科院分区：
文献类型：
--
作者：
Sutter, CH;Laughner, E;Semenza, GL
缺氧诱导因子1（HIF-1）是一种转录因子，在哺乳动物中介导细胞和系统对减少的O-2可用性的稳态应答，包括血管生成。红细胞生成和糖酵解。HIF-1活性受O-2调节的HIF-1 α亚基的表达控制。在非缺氧条件下，HIF-1 α蛋白受到泛素化和蛋白酶体降解。在这里，我们报告的错义突变和/或缺失涉及几个不同的区域HIF-1 α的组成型表达和转录活性在非缺氧细胞的结果。我们证明缺氧导致HIF-1 α的泛素化降低，错义突变通过阻断泛素化在非缺氧条件下增加HIF-1 α的表达。
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O-2 availability in mammals, including angiogenesis. erythropoiesis, and glycolysis. HIF-1 activity is controlled by the O-2-regulated expression of the HIF-1 alpha subunit, Under nonhypoxic conditions, HIF-1 alpha protein is subject to ubiquitination and proteasomal degradation. Here we report that missense mutations and/or deletions involving several different regions of HIF-1 alpha result in constitutive expression and transcriptional activity in nonhypoxic cells. We demonstrate that hypoxia results in decreased ubiquitination of HIF-1 alpha and that missense mutations increase HIF-1 alpha expression under nonhypoxic conditions by blocking ubiquitination.