CGGBP1 is a nuclear and midbody protein regulating abscission
CGGBP1 is a nuclear and midbody protein regulating abscission
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DOI：
10.1016/j.yexcr.2010.08.019
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发表时间：
2011-01-15
影响因子：
3.7
通讯作者：
Westermark, Bengt
中科院分区：
文献类型：
--
作者：
Singh, Umashankar;Westermark, Bengt
脱落标志着细胞分裂的完成，它的失败与胞质分裂延迟甚至四倍体有关。异常脱落和随之而来的倍性变化可能是包括癌症在内的各种疾病的基础。中体是末期细胞间桥形成的一种瞬时结构，含有多种参与脱落的蛋白质，包括极光蛋白B(Aurora Kinase B，AURKB)。我们在此报道了转录抑制蛋白CGG三联重复结合蛋白1(CGGBP1)在正常人成纤维细胞中的意外表达模式和功能。我们发现，CGGBP1是一种染色质相关蛋白，以类似于AURKB的方式反式定位到纺锤体中区和中体。CGGBP1缺失导致细胞周期阻滞于G2期，表现为细胞无法进行有丝分裂，同时也减少了进入S期的时间。与其在中体中的存在一致，活体显微镜显示CGGBP1缺乏导致脱落时有丝分裂失败，导致四倍体，这可以通过CGGBP1的过表达来挽救。这些结果表明，CGGBP1是一种真正的中体蛋白，通常需要正常的脱落和有丝分裂。(C)2010 Elsevier Inc.保留所有权利。
Abscission marks the completion of cell division and its failure is associated with delayed cytokinesis and even tetraploidization. Aberrant abscission and consequential ploidy changes can underlie various diseases including cancer. Midbody, a transient structure formed in the intercellular bridge during telophase, contains several proteins including Aurora kinase B (AURKB), which participate in abscission. We report here an unexpected expression pattern and function of the transcription repressor protein CGG triplet repeat-binding protein 1 (CGGBP1), in normal human fibroblasts. We show that CGGBP1, a chromatin-associated protein, trans-localizes to spindle midzone and midbodies in a manner similar to that of AURKB. CGGBP1 depletion resulted in a cell cycle block at G2, characterized by failure of cells to undergo mitosis and also reduced entry into S phase. Consistent with its presence in the midbodies, live microscopy showed that CGGBP1 deficiency caused mitotic failure at abscission resulting in tetraploidy, which could be rescued by CGGBP1 overexpression. These results show that CGGBP1 is a bona fide midbody protein required for normal abscission and mitosis in general. (C) 2010 Elsevier Inc. All rights reserved.