A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis
A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis
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DOI：
10.1083/jcb.140.5.991
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发表时间：
1998-03-09
影响因子：
7.8
通讯作者：
Earnshaw, WC
中科院分区：
文献类型：
--
作者：
Mackay, AM;Ainsztein, AM;Earnshaw, WC
INCENP是一种紧密结合的染色体蛋白，在中期/后期转换时转移到纺锤体中间区。在这里，我们表明，INCENP截断突变体（INCENP 382 -839）与微管，但不结合染色体，并在整个有丝分裂的整个纺锤体的涂层。此外，先前显示INCENP截短突变体（INCENP 43 -839）在后期不转移到纺锤体（Mackay，A.M.，D.M，Eckley，C. Chue和W.C.恩萧1993. J. Cell Biol.123：373-385）结合染色体，但不能靶向着丝粒。因此，与染色体，特别是与着丝粒的结合似乎是INCENP在后期靶向正确的纺锤体亚结构域所必需的。靶向着丝粒但缺乏微管结合区的INCENP截短突变体（INCENP 1 -405）获得了强的显性阴性特征。INCENP 1 -405干扰前中期染色体排列和胞质分裂的完成，INCENP 1 -405显然通过从着丝粒置换内源性nous蛋白来发挥其作用。这些实验提供了这种染色体蛋白质和胞质分裂之间意外联系的证据，并表明INCENP的功能之一可能是整合有丝分裂的染色体和细胞骨架事件。
INCENP is a tightly bound chromosomal protein that transfers to the spindle midzone at the metaphase/anaphase transition. Here, we show that an INCENP truncation mutant (INCENP382-839) associates with microtubules but does not bind to chromosomes, and coats the entire spindle throughout mitosis. Furthermore, an INCENP truncation mutant (INCENP43-839) previously shown not to transfer to the spindle at anaphase (Mackay, A.M., D.M, Eckley, C. Chue, and W.C. Earnshaw. 1993. J. Cell Biol. 123:373-385), is shown here to bind chromosomes, but is unable to target to the centromere, Thus, association with the chromosomes, and specifically with centromeres, appears to be essential for INCENP targeting to the correct spindle subdomain at anaphase, An INCENP truncation mutant (INCENP1-405) that targets to centromeres but lacks the microtubule association region acquires strong dominant-negative characteristics. INCENP1-405 interferes with both prometaphase chromosome alignment and the completion of cytokinesis, INCENP1-405 apparently exerts its effect by displacing the endogenous nous protein from centromeres. These experiments provide evidence of an unexpected link between this chromosomal protein and cytokinesis, and suggest that one function of INCENP may be to integrate the chromosomal and cytoskeletal events of mitosis.