TRIM8 modulates STAT3 activity through negative regulation of PIAS3
TRIM8 modulates STAT3 activity through negative regulation of PIAS3
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DOI：
10.1242/jcs.068981
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
Hatakeyama, Shigetsugu
中科院分区：
文献类型：
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作者：
Okumura, Fumihiko;Matsunaga, Yui;Hatakeyama, Shigetsugu
TRIM 8是蛋白质家族的成员，其通过由三重基序组成的共同结构域结构的存在来定义：环指，一个或两个B盒结构域和卷曲螺旋基序。在这里，我们表明TRIM 8与活化的STAT 3（PIAS 3）的蛋白质抑制剂相互作用，其抑制IL-6依赖的STAT 3活化。TRIM 8的异位表达通过泛素-蛋白酶体途径降解PIAS 3或将PIAS 3从细胞核中排除来消除PIAS 3对STAT 3的负面作用。此外，TRIM 8在NIH 3 T3细胞中的表达增强Src依赖性肿瘤发生。这些发现表明TRIM 8通过抑制PIAS 3的功能来增强STAT 3依赖性信号通路。
TRIM8 is a member of the protein family defined by the presence of a common domain structure composed of a tripartite motif: a RING-finger, one or two B-box domains and a coiled-coil motif. Here, we show that TRIM8 interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. Ectopic expression of TRIM8 cancels the negative effect of PIAS3 on STAT3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus. Furthermore, expression of TRIM8 in NIH3T3 cells enhances Src-dependent tumorigenesis. These findings indicate that TRIM8 enhances the STAT3-dependent signal pathway by inhibiting the function of PIAS3.