iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation.
iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation.
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DOI：
10.1038/s41419-018-0561-6
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发表时间：
2018-05-01
影响因子：
9
通讯作者：
Wang C
中科院分区：
文献类型：
--
作者：
Gao K;Zhang Y;Shi Q;Zhang J;Zhang L;Sun H;Jiao D;Zhao X;Tao H;Wei Y;Wang Y;Saiyin H;Zhao SM;Li Y;Zhang P;Wang C
胞质分裂是细胞分裂的最后一步，通过切断连接两个子细胞的胞间桥梁而结束。由于胞质分裂失败与多种人类疾病有关，因此对胞质分裂完成的严格调控是必不可少的。在这里，我们报告iASPP是p53(ASPP)家族中的一员，是细胞正常分裂所必需的。IASPP耗竭导致中体结构异常和胞质分裂失败。我们用蛋白质亲和纯化的方法鉴定了iASPP的功能伙伴。我们发现iASPP与一个重要的细胞动力学脱落调节因子55 kDa的中心体蛋白(CEP55)有关。机械上，iASPP作为PP1靶向亚基，促进PP1和CEP55之间的相互作用，并在有丝分裂后期去除PLK1介导的CEP55中Ser436的磷酸化。后一步对于及时将CEP55招募到中体至关重要。目前的观察揭示了以前未知的iASPP在细胞质分裂中的功能。这一功能反过来可能有助于iASPP在肿瘤发展和遗传性疾病中的作用。
Cytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the apoptosis-stimulating proteins of p53 (ASPP) family, is required for proper cell division. iASPP depletion results in abnormal midbody structure and failed cytokinesis. We used protein affinity purification methods to identify the functional partners of iASPP. We found that iASPP associates with centrosomal protein of 55 kDa (CEP55), an important cytokinetic abscission regulator. Mechanically, iASPP acts as a PP1-targeting subunit to facilitate the interaction between PP1 and CEP55 and to remove PLK1-mediated Ser436 phosphorylation in CEP55 during late mitosis. The latter step is critical for the timely recruitment of CEP55 to the midbody. The present observations revealed a previously unrecognized function of iASPP in cytokinesis. This function, in turn, likely contributes to the roles of iASPP in tumor development and genetic diseases.
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影响因子：
11.1
作者：
Falik-Zaccai TC;Barsheshet Y;Mandel H;Segev M;Lorber A;Gelberg S;Kalfon L;Ben Haroush S;Shalata A;Gelernter-Yaniv L;Chaim S;Raviv Shay D;Khayat M;Werbner M;Levi I;Shoval Y;Tal G;Shalev S;Reuveni E;Avitan-Hersh E;Vlodavsky E;Appl-Sarid L;Goldsher D;Bergman R;Segal Z;Bitterman-Deutsch O;Avni O
通讯作者：
Avni O
影响因子：
64.5
作者：
Bouchoux, Celine;Uhlmann, Frank
通讯作者：
Uhlmann, Frank
影响因子：
56.9
作者：
Carlton, Jez G.;Martin-Serrano, Juan
通讯作者：
Martin-Serrano, Juan
影响因子：
4.8
作者：
Llanos, Susana;Royer, Christophe;Lu, Xin
通讯作者：
Lu, Xin
DOI：
10.1073/pnas.1408111112
发表时间：
2015-03-03
影响因子：
11.1
作者：
Notari, Mario;Hu, Ying;Lu, Xin
通讯作者：
Lu, Xin