Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity
Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity
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DOI：
10.1016/j.bbrc.2005.11.076
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发表时间：
2006-01-20
影响因子：
3.1
通讯作者：
Kamitani, T
中科院分区：
文献类型：
--
作者：
Wada, K;Tanji, K;Kamitani, T
UnpEL（也称为Usp4或Unph）是一种致癌蛋白，因为其与强启动子一起表达导致注射到裸鼠中的NIH 3T3细胞的致瘤性转化。尽管UnpEL的结构是去泛素化酶的结构，但其在哺乳动物细胞中的确切功能和UnpEL介导的肿瘤发生机制都不清楚。在这里，我们表明，UnpEL功能作为一个去泛素化酶在人类HEK293 T细胞和其异肽酶活性去缀合泛素特异性从UnpEL相互作用蛋白Ro52。我们进一步表明，UnpEL易位到细胞质棒状结构和共定位Ro52时Ro52在HEK293细胞中过表达。这些结果表明，UnpEL与Ro52的未泛素化形式共定位于细胞质杆状结构，在那里它保持Ro52未泛素化。Ro52的持续去泛素化可能参与肿瘤的发生。(c)2005年爱思唯尔公司All rights reserved.
UnpEL (also known as Usp4 or Unph) is an oncogenic protein, because its expression with a strong promoter results in the tumorigenic transformation of NIH3T3 cells injected into nude mice. Although the structure of UnpEL is that of a deubiquitinating enzyme, neither its precise function in mammalian cells nor the mechanism of UnpEL-mediated tumorigenesis is known. Here, we show that UnpEL functions as a deubiquitinating enzyme in human HEK293T cells and its isopeptidase activity deconjugates ubiquitin specifically from a UnpEL-interacting protein Ro52. We further show that UnpEL translocates to the cytoplasmic rod-like structures and colocalizes with Ro52 when Ro52 is overexpressed in HEK293 cells. These results suggest that UnpEL colocalizes with the unubiquitinated form of Ro52 to the cytoplasmic rod-like structures, where it keeps Ro52 unubiquitinated. The continuous deubiquitination of Ro52 might be involved in tumorigenesis. (c) 2005 Elsevier Inc. All rights reserved.