Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner.
Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner.
复制标题
DOI：
10.15252/embr.201438850
复制
发表时间：
2014-12
期刊：
影响因子：
7.7
通讯作者：
Komander D
中科院分区：
文献类型：
--
作者：
Bremm A;Moniz S;Mader J;Rocha S;Komander D
转录因子HIF-1α对于细胞快速适应低氧水平（缺氧）至关重要。HIF-1α在癌症中经常失调，与患者预后不良相关。在这里，我们证明了去泛素化酶Cezanne调节HIF-1α稳态。Cezanne的缺失降低了HIF-1α靶基因的表达，因为HIF-1α蛋白水平降低。令人惊讶的是，尽管Cezanne调节的HIF-1α降解依赖于肿瘤抑制因子pVHL，但羟化酶和蛋白酶体活性是不稳定的。我们的数据表明，Cezanne对HIF-1α蛋白的稳定性至关重要，Cezanne的缺失刺激HIF-1α通过蛋白酶体非依赖性途径降解，可能是通过分子伴侣介导的自噬。翻译后修饰、蛋白质水解和蛋白质组学;信号转导
The transcription factor HIF-1α is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1α is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1α homeostasis. Loss of Cezanne decreases HIF-1α target gene expression due to a reduction in HIF-1α protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1α depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1α protein stability and that loss of Cezanne stimulates HIF-1α degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy. Subject Categories Post-translational Modifications, Proteolysis & Proteomics; Signal Transduction