BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma
BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma
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BAP1 通过稳定肾细胞癌中的 DIDO1 来维持染色体稳定性
DOI：
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发表时间：
2020
影响因子：
5.3
通讯作者：
Zhonghua Yang
中科院分区：
文献类型：
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作者：
Jiantao Xiao;Ruhan Zhang;Jingtao Peng;Zhonghua Yang
BRCA 1相关蛋白1（BAP 1）是去泛素化酶的泛素C-末端水解酶家族的成员，并参与转录调控。5%-15%的肾透明细胞癌（ccRCC）患者的BAP 1基因发生突变，这表明BAP 1是一种肿瘤抑制因子，肾透明细胞癌是最常见的肾癌形式。然而，BAP 1是否影响表达野生型（WT）BAP 1的ccRCC肿瘤的进展尚不清楚。在这里，我们鉴定了艾德DIDO 1作为BAP 1的良好底物。DIDO 1是中心体蛋白的组成部分，在纺锤体组装中起着重要作用。BAP 1与DIDO 1结合并通过去泛素化稳定DIDO 1。BAP 1部分通过DIDO 1促进染色体稳定性。在ccRCC组织中，BAP 1和DIDO 1表达之间存在正相关性，艾德。ccRCC中BAP 1缺失和DIDO 1蛋白表达的下调与不良临床病理特征相关。这项研究揭示了一种涉及BAP 1调节DIDO 1稳定性的新机制，结果也为了解BAP 1突变与ccRCC中染色体不稳定性之间的关系提供了见解。
BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C-terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The BAP1 gene is mutated in 5%-15% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, which suggests that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing wildtype (WT) BAP1 is unclear. Here, we identified DIDO1 as a bona fide substrate for BAP1. DIDO1 is a component of the centrosome proteins and plays an essential role in spindle assembly. BAP1 binds to DIDO1 and stabilizes DIDO1 through de-ubiquitination. BAP1 contributes to chromosome stability partially via DIDO1. A positive correlation was identified between BAP1 and DIDO1 expression in ccRCC tissues. Downregulation of both BAP1-loss and DIDO1 protein expression in ccRCC was associated with adverse clinicopathological features. This study revealed a novel mechanism involving BAP1 in the regulation of DIDO1 stability, and the results also provide insight into the relationship between BAP1 mutations and chromosome instability in ccRCC.