Depaux A, Regnier-Ricard F, Germani A, Varin-Blank N
Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France.
Oncogene. 2007 Oct 11;26(46):6665-76. doi: 10.1038/sj.onc.1210486. Epub 2007 May 28.
Protein inhibitor of activated STAT (Pias) and human homologues of seven in absentia (hSiah) proteins both exhibit properties of ubiquitin-family peptides conjugating enzymes. Pias present E3-ligase activity for small ubiquitin-related modifiers (Sumo) covalent attachment to their targets. This post-translational modification is responsible for the activation of different transcription factors such as AP1. HSiah proteins possess ubiquitin-E3-ligase activity that triggers their partners to proteasomal-dependent degradation. The present study identifies Pias as a new hSiah2-interacting protein. We demonstrate that hSiah2 regulates specifically the proteasome-dependent degradation of Pias proteins. On reverse, Pias does not prevent hSiah2 degradation. We provide evidences for hSiah2-dependent degradation of Pias as being a mechanism in the regulation of c-jun N-terminal kinase-activating pathways. This report describes a new interconnection between sumoylation and ubiquitination pathways by regulating the levels of the E3-ligases available for these processes.
信号转导子与转录激活子激活蛋白的蛋白抑制剂（Pias）和人七号缺席同源蛋白（hSiah）均表现出泛素家族肽缀合酶的特性。Pias具有E3连接酶活性，可将小泛素相关修饰物（Sumo）共价连接至其靶标。这种翻译后修饰负责激活不同的转录因子，如AP1。hSiah蛋白具有泛素E3连接酶活性，可触发其伴侣蛋白通过蛋白酶体依赖性途径降解。本研究鉴定出Pias是一种新的与hSiah2相互作用的蛋白。我们证明hSiah2特异性调节Pias蛋白的蛋白酶体依赖性降解。相反，Pias并不阻止hSiah2的降解。我们提供证据表明，hSiah2依赖性的Pias降解是调节c-jun氨基末端激酶激活途径的一种机制。本报告描述了通过调节可用于这些过程的E3连接酶水平，在Sumo化和泛素化途径之间建立的一种新联系。
