癌症高表达蛋白——Hec1在纺锤体组装检查点中的作用
瞿 颖 ,刘炳亚*
上海第二医科大学附属瑞金医院,上海消化外科研究所,上海 200025

摘 要:
摘 要:细胞增殖依赖于细胞分裂前染色体的复制及随后的姐妹染色单体分离到达两极。纺锤体组装检查点具有确保染色体信息传递保真性的作用,检查点的缺失可能导致染色体的分离异常和肿瘤形成。癌症高表达蛋白(Hec1)通过与调控G2/M期的蛋白间的相互作用而在染色体的分离中发挥重要作用。Hec1与Nuf2的复合物,在G2/M期与动粒相结合,Hec1的缺失将导致严重的染色体分离错误。Hec1具有召集Mps1和Mad1/Mad2复合物结合到动粒上的作用,这种结合可以激活纺锤体组装检查点途径中非常重要的APCCdc20途径。但是Hec1、Mps1、Mad1三者之间的相互作用仍未明了。Hec1还可以通过与26S蛋白酶复合物的不同亚基结合调控其功能。Hec1是一种丝氨酸磷酸化蛋白,其磷酸化是由Nek2在G2/M期完成的。
关键词:癌症高表达蛋白;纺锤体组装检查点;有丝分裂;动粒

The role of Hec1 in the network of spindle assembly checkpoint
QU Ying, LIU Bing-Ya*
Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China

Abstract: Abstract:  Cell proliferation depends on the duplication of chromosomes followed by the segregation of sister chromatids to opposite poles of the cell prior to cell division.  The spindle assembly checkpoint plays a central role in the fidelity of chromosome transmission by ensuring that anaphase is initiated only after kinetochore-microtubule associations of all sister chromatid pairs are complete. Checkpoint failure may lead to chromosome mis-segregation and may contribute to tumorigensis. Hec1(highly expressed in cancer) plays essential roles in chromosome segregation by interacting with several proteins that modulate the G2/M phase. Binding with Nuf2, Hec1 localizes to kinetochores at G2/M phase, its inactivation leads to severe and lethal chromosomal segregation errors.  It is reported that Hec1 was required for the recruitment of Mps1 and Mad1/Mad2 complex to kinetochore which initiating the important APCCdc20 pathway.  But the interactions between Hec1,and Mps1 and Mad1 are not very clear.  Hec1 regulates 26S proteasome activity through interaction with some of its subunits.  Hec1 is a serine phosphoprotein and its phosphorylation is by Nek2 during G2/M phase.
Key words:  Hec1; spindle assembly checkpoint; mitosis; kinetochore

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