Integrin signaling via FAK-Src controls cytokinetic abscission by decelerating PLK1 degradation and subsequent recruitment of CEP55 at the midbody.
Integrin signaling via FAK-Src controls cytokinetic abscission by decelerating PLK1 degradation and subsequent recruitment of CEP55 at the midbody.
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DOI：
10.18632/oncotarget.9003
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Johansson S
中科院分区：
文献类型：
--
作者：
Kamranvar SA;Gupta DK;Huang Y;Gupta RK;Johansson S
粘附到细胞外基质是细胞周期进展通过G1期和完成正常粘附细胞的胞质分裂所必需的。癌细胞获得不依赖于锚定增殖的能力，这是恶性转化细胞的特征。然而，这种逃避正常控制机制的分子机制仍不清楚。本研究旨在确定调节非转化人成纤维细胞胞质分裂的粘附诱导反应。细胞质分裂的粘附依赖性控制被发现发生在接近分裂的晚期，在此期间，运输所需的内体分选复合物（ESCRT）切断了连接两个新生子细胞的细胞间桥。CEP 55，一种参与解离过程的关键蛋白，定位于粘附和非粘附成纤维细胞的中间体，但它不能有效地募集阿利克斯，TSG 101，因此ESCRT-III亚基CHMP 4 B在非粘附细胞中缺失。PLK 1是一种阻止CEP 55过早募集到中间体的激酶，在非贴壁细胞中从该位点更快地消失。FAK-Src信号通路下游的整合素介导的细胞粘附被发现减速PLK 1降解和CEP 55的积累在中间体。这些数据确定PLK 1和CEP 55的调节是整合素对细胞动力学抑制施加控制的步骤。
Adhesion to extracellular matrix is required for cell cycle progression through the G1 phase and for the completion of cytokinesis in normal adherent cells. Cancer cells acquire the ability to proliferate anchorage-independently, a characteristic feature of malignantly transformed cells. However, the molecular mechanisms underlying this escape of the normal control mechanisms remain unclear. The current study aimed to identify adhesion-induced reactions regulating the cytokinesis of non-transformed human fibroblasts. The adhesion-dependent control of cytokinesis was found to occur at a late stage close to the abscission, during which the endosomal sorting complex required for transport (ESCRT) severs the thin intercellular bridge connecting two nascent daughter cells. CEP55, a key protein involved in the abscission process, was localized at the midbody in both adherent and non-adherent fibroblasts, but it was unable to efficiently recruit ALIX, TSG101, and consequently the ESCRT-III subunit CHMP4B was missing in the non-adherent cells. PLK1, a kinase that prevents premature recruitment of CEP55 to the midbody, disappeared from this site more rapidly in the non-adherent cells. A FAK-Src signaling pathway downstream of integrin-mediated cell adhesion was found to decelerate both PLK1 degradation and CEP55 accumulation at the midbody. These data identify the regulation of PLK1 and CEP55 as steps where integrins exert control over the cytokinetic abscission.
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影响因子：
4.8
作者：
Kadare, Gress;Gervasi, Nicolas;Girault, Jean-Antoine
通讯作者：
Girault, Jean-Antoine
DOI：
10.1083/jcb.200309035
发表时间：
2004-01-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lindon C;Pines J
通讯作者：
Pines J
影响因子：
56.9
作者：
Guizetti, Julien;Schermelleh, Lothar;Gerlich, Daniel W.
通讯作者：
Gerlich, Daniel W.
影响因子：
112.7
作者：
Iskratsch, Thomas;Wolfenson, Haguy;Sheetz, Michael P.
通讯作者：
Sheetz, Michael P.
DOI：
10.1083/jcb.201008108
发表时间：
2010-11-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bastos RN;Barr FA
通讯作者：
Barr FA