ACTIVATION OF THE NIMA PROTEIN-KINASE PLAYS A UNIQUE ROLE DURING MITOSIS THAT CANNOT BE BYPASSED BY ABSENCE OF THE BIME CHECKPOINT
ACTIVATION OF THE NIMA PROTEIN-KINASE PLAYS A UNIQUE ROLE DURING MITOSIS THAT CANNOT BE BYPASSED BY ABSENCE OF THE BIME CHECKPOINT
复制标题
DOI：
10.1002/j.1460-2075.1991.tb07810.x
复制
发表时间：
1991-09-01
期刊：
影响因子：
11.4
通讯作者：
OSMANI, SA
中科院分区：
文献类型：
--
作者：
OSMANI, AH;ODONNELL, K;OSMANI, SA
Nim A的突变可逆地阻止细胞在G2晚期，Nim A的过度表达促进了过早的有丝分裂。在这里，我们证明了Nim A(指定为NIMA)的产物具有蛋白激酶活性，可以磷酸化β-酪蛋白，但不能磷酸化组蛋白。NIMA激酶活性受细胞周期调控，在有丝分裂时是S期细胞的20倍。在G2中，NIMA的激活通常需要启动染色体凝聚，使纺锤体微管成核，并允许MPM-2特异性有丝分裂磷酸化。当bim E基因突变时，在没有激活的NIMA的情况下，所有这三种有丝分裂事件都可以发生(Bim E7)。然而，bim E7突变不能完全绕过有丝分裂过程中对Nim A的要求，因为在没有NIMA激活的情况下进入有丝分裂会导致重大的有丝分裂缺陷，影响核膜的组织和有丝分裂纺锤体。因此，尽管Nim A在有丝分裂过程中发挥了重要但有限的作用，但Nim A的突变阻止了所有的有丝分裂。因此，我们认为Nim A的突变阻止了有丝分裂的启动，这是由于bim E负向介导的检查点停止所致。检查点确保在NimA有丝分裂激活之前不会启动有丝分裂。
Mutation of nim A reversibly arrests cells in late G2 and nim A overexpression promotes premature mitosis. Here we demonstrate that the product of nim A (designated NIMA) has protein kinase activity that can phosphorylate beta-casein but not histone proteins. NIMA kinase activity is cell cycle regulated being 20-fold higher at mitosis when compared to S-phase arrested cells. NIMA activation is normally required in G2 to initiate chromosome condensation, to nucleate spindle pole body microtubules, and to allow an MPM-2 specific mitotic phosphorylation. All three of these mitotic events can occur in the absence of activated NIMA when the bim E gene is mutated (bim E7). However, the bim E7 mutation cannot completely bypass the requirement for nim A during mitosis as entry into mitosis in the absence of NIMA activation results in major mitotic defects that affect both the organization of the nuclear envelope and mitotic spindle. Thus, although nim A plays an essential but limited role during mitosis, mutation of nim A arrests all of mitosis. We therefore propose that mutation of nim A prevents mitotic initiation due to a checkpoint arrest that is negatively mediated by bim E. The checkpoint ensures that mitosis is not initiated until NIMA is mitotically activated.