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      Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma.

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          Abstract

          Characterization of the exome and genome of carcinoma (ccRCC) by next-generation sequencing identified numerous genetic alternations. BRCA1-associated protein-1 (BAP1) was identified as one of the most frequently mutated genes in ccRCC, suggesting that BAP1 is a potential key driver for ccRCC cancer initiation and progression. However, how BAP1 mutations contribute to ccRCC remains to be elucidated. BAP1 is a nuclear de-ubiquitinating enzyme and cleaves the ubiquitin chain from the substrates. Here, we identified MCRS1 as a bona fide substrate for BAP1. MCRS1 is a component of the centrosome proteins, and plays an essential role in spindle assembly. BAP1 binds to MCRS1 and stabilizes MCRS1 by de-ubiquitination. BAP1 contributes to chromosome stability partially via MCRS1. A positive correlation was identified between BAP1 and MCRS1 expression in ccRCC tissues. Both BAP1 loss and MCRS1 down-regulation in ccRCC were associated with adverse clinicopathological features. This study revealed a novel mechanism for BAP1 involved in MCRS1 stability regulation, and provided insight in understanding the relationship between BAP1 mutations and chromosome instability in ccRCC.

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          Author and article information

          Journal
          Cancer Lett.
          Cancer letters
          Elsevier BV
          1872-7980
          0304-3835
          Dec 01 2015
          : 369
          : 1
          Affiliations
          [1 ] Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 100 Haining Road, Shanghai 200080, China.
          [2 ] Department of Urology, Inner Mongolia Autonomous Region Peoples Hospital, 20 Zhaowuda Road, Hohhot 010017, China.
          [3 ] State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China.
          [4 ] State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005 Songhu Road, Shanghai 200433, China. Electronic address: chenjiwang@fudan.edu.cn.
          [5 ] Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, 100 Haining Road, Shanghai 200080, China. Electronic address: jief67@sina.com.
          Article
          S0304-3835(15)00542-X
          10.1016/j.canlet.2015.08.013
          26300492
          3b1c4509-6381-4855-b4b1-7c38f885ad02
          History

          Chromosome instability,BAP1,MCRS1,De-ubiquitination,Clear cell renal cell carcinoma

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