STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH
STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH
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DOI：
10.1016/j.bbrc.2006.10.068
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发表时间：
2006-12-22
影响因子：
3.1
通讯作者：
Jeon, Hyesung
中科院分区：
文献类型：
--
作者：
Kim, Man Su;Kim, Jeom-A;Jeon, Hyesung
信号转导衔接子分子（STAM）与肝细胞生长因子调节酪氨酸激酶底物（Hrs）复合，在多泡体（MVB）信号转导通路中对货物蛋白进行分选。STAM SH 3结构域相关分子（AMSH）是一种含锌的泛素异肽酶，被认为通过与STAM结合在泛素介导的降解中发挥作用。我们发现AMSH需要Px（V/I）（D/N）RxxKP序列的构象才能与STAM的SH 3结构域结合，其亲和力接近7 μ M，并且AMSH的分离的C-末端结构域具有异肽酶活性。当泛素与STAM结合时，AMSH的去泛素化得到辅助，STAM可以同时与AMSH结合。对K63连接的遍在蛋白具有特异性。AMSH的这种促进的泛素加工活性可能意味着通过STAM结合进行分选和降解的独特调节机制。(c)2006年爱思唯尔公司All rights reserved.
Signal transducing adaptor molecule (STAM) complexed with hepatocyte growth factor regulated tyrosine kinase substrate (Hrs) works on sorting of cargo proteins in multivesicular body (MVB) pathway. Associated molecule with SH3 domain of STAM (AMSH), a zinc-containing ubiquitin isopeptidase, is thought to play a role in regulation of ubiquitin-mediated degradation by binding to STAM. We have found that AMSH requires the conformation of Px(V/I)(D/N)RxxKP sequence to bind SH3 domain of STAM with similar to 7 mu M affinity, and that the isolated C-terminal domain of AMSH contains the isopeptidase activity. Deubiquitination by AMSH was assisted when ubiquitins were bound to STAM which can bind to AMSH simultaneously. With the specificity toward K63-linked ubiquitins. this facilitated ubiquitin processing activity of AMSH may imply a distinct regulatory mechanism for sorting and degradation through STAM binding. (c) 2006 Elsevier Inc. All rights reserved.