The E3 ubiquitin ligase Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability
The E3 ubiquitin ligase Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability
复制标题
E3泛素连接酶Itch和Yap1在ASPP2蛋白稳定性的调节中具有拮抗作用。
DOI：
10.1016/j.febslet.2014.11.030
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发表时间：
2015-01-02
期刊：
影响因子：
3.5
通讯作者：
Wang, Chenji
中科院分区：
文献类型：
--
作者：
Gao, Kun;An, Jian;Wang, Chenji
ASPP 2是一种重要的肿瘤抑制蛋白，可促进p53依赖和非依赖的细胞凋亡。然而，目前还不清楚ASPP2蛋白是如何调节的。在这里，我们将Itch鉴定为ASPP 2的E3泛素连接酶。瘙痒与ASPP 2相互作用并介导其在体内的降解和泛素化。ASPP 2的PPXY基序与Itch的WW结构域相互作用。Yap1与Itch竞争结合ASPP2，并阻止Itch介导的ASPP2降解和泛素化。总之，这些观察结果表明，Itch和Yap 1通过竞争ASPP 2的翻译后调节机制在ASPP 2蛋白稳定性的调节中具有拮抗作用。(C)2014年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
ASPP2 is an important tumor suppressor protein promoting p53-dependent and-independent apoptosis. However, it has been unclear how ASPP2 protein is regulated. Here, we identified Itch as the E3 ubiquitin ligase for ASPP2. Itch interacts with ASPP2 and mediates its degradation and ubiquitination in vivo. The PPXY motif of ASPP2 interacts with the WW domains of Itch. Yap1 competes with Itch for binding to ASPP2, and prevents Itch-mediated degradation and ubiquitination of ASPP2. Together, these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post-translational regulatory mechanism of ASPP2. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.