Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells
Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells
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DOI：
10.1016/j.virol.2007.06.024
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发表时间：
2007-11-10
期刊：
影响因子：
3.7
通讯作者：
Randall, R. E.
中科院分区：
文献类型：
--
作者：
Precious, B. L.;Carlos, T. S.;Randall, R. E.
已提出了parainfluenza病毒5（P1V5；以前是SV5）的STAT1降解的动态模型。在其中，V蛋白充当链接DDB1的两分衔接子，DDB1是细胞SCF样的泛素E3连接酶复合物的组成部分，与STAT2与STAT2相结合，后者又结合了STAT1并将Stati与E3 Ligase络合物呈现到E3 Ligase络合物以进行泛素化和随后的降解。此外，似乎复合物中的Stati损失导致V对STAT2的亲和力降低，因此Stat2要么从V中解离或被STAT1/STAT2复合物取代，从而促进了含DDB1/P1V5 V的循环，其中含有E3复合物的E3复合物。 STAT1泛素化和降解。通过确定IFN处理的2FFGH细胞中存在的V，DDB 1，Stati和STAT2的分子的近似数，我们为STAT 1降解的这种动态模型提供了其他证据。这些结果表明，（i）在经过IFN处理的单元中（i），STAT2的STAT2少4倍，而DDB I的DDB I比每个细胞的STATL少15倍，因此DDB I和STAT2必须反复获取更多的STAT 1，以使降解完成，以完成降解，以完成，从而完成。 （ii）在没有病毒或细胞蛋白的情况下，每个细胞的大约600个分子的V蛋白可以靶向多达120,000个STAT1分子降解。 合成。讨论了这种机制在拆除IFN引起的抗病毒细胞状态的能力方面的重要性。 （c）2007 Elsevier Inc.保留所有权利。
A dynamic model of STAT1 degradation by the V protein of parainfluenza virus 5 (P1V5; formerly SV5) has been proposed. In it, the V protein functions as a bipartite adaptor linking DDB1, a component of a cellular SCF-like ubiquitin E3 ligase complex, to STAT2, which in turn binds STAT1 and presents STATI to the E3 ligase complex for ubiquitination and subsequent degradation. Furthermore, it appears that loss of STATI from the complex results in decreased affinity of V for STAT2 such that STAT2 either dissociates from V or is displaced by STAT1/STAT2 complexes, facilitating the cycling of the DDB1/P1V5 V containing E3 complex for further rounds of STAT1 ubiquitination and degradation. By determining the approximate number of molecules of V, DDB 1, STATI and STAT2 present in IFN-treated 2fFGH cells, we provide additional evidence for this dynamic model of STAT 1 degradation. These results show that (i) in IFN-treated cells there is approximately 4-fold less STAT2 and 15-fold less DDB I than STATl per cell and thus DDB I and STAT2 must repeatedly acquire more STAT 1 for degradation to go to completion, and (ii) approximately 600 molecules of V protein per cell can target as many as 120,000 molecules of STAT1 for degradation in the absence of either viral or cellular protein synthesis. The importance of this mechanism in terms of the ability of the virus to dismantle the IFN-induced anti-viral state of cells is discussed. (C) 2007 Elsevier Inc. All rights reserved.