Protein kinase D1 inhibition interferes with mitosis progression.
Protein kinase D1 inhibition interferes with mitosis progression.
复制标题
蛋白激酶 D1 抑制会干扰有丝分裂进程。
DOI：
10.1002/jcp.28651
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发表时间：
2019
影响因子：
5.6
通讯作者：
Rey,Osvaldo
中科院分区：
文献类型：
--
作者：
Martínez-León,Eduardo;Amable,Gastón;Jácamo,Rodrigo;Picco,MaríaElisa;Anaya,Laura;Rozengurt,Enrique;Rey,Osvaldo
蛋白激酶D1（PKD 1）在信号转导、细胞增殖、膜运输和癌症中起着重要作用，但迄今为止，大多数研究主要集中在PKD 1在细胞分裂间期的功能，对PKD 1在细胞分裂中的作用知之甚少。我们以前证明，在有丝分裂PKD 1被激活，并与中心体，纺锤体和中间体。然而，这些观察结果并没有解决PKD 1是否与有丝分裂调控相关。因此，我们使用快速作用的PKD特异性抑制剂来检查PKD 1对有丝分裂事件顺序的贡献。我们发现，尽管PKD 1过表达不影响有丝分裂进程，但两种结构无关的抑制剂（kb NB 142 - 70和CRT 0066101）对其催化活性的抑制诱导了中期至后期转换时间的显著延迟。在有丝分裂过程中PKD 1抑制也产生异常纺锤体的外观，染色体排列的缺陷，分离以及凋亡。因此，这些观察结果表明PKD 1活性与有丝分裂调节相关。
Protein kinase D1 (PKD1) plays a vital role in signal transduction, cell proliferation, membrane trafficking, and cancer; however, the majority of the studies up to date had centered primarily on PKD1 functions in interphase, very little is known about its role during cell division. We previously demonstrated that during mitosis PKD1 is activated and associated with centrosomes, spindles, and midbodies. However, these observations did not address whether PKD1 was associated with mitosis regulation. Accordingly, we used rapidly acting PKD‐specific inhibitors to examine the contribution of PKD1 the sequence of events in mitosis. We found that although PKD1 overexpression did not affect mitosis progression, suppression of its catalytic activity by two structurally unrelated inhibitors (kb NB 142‐70 and CRT 0066101) induced a significant delay in metaphase to anaphase transition time. PKD1 inhibition during mitosis also produced the appearance of abnormal spindles, defects in chromosome alignment, and segregation as well as apoptosis. Thus, these observations indicate that PKD1 activity is associated with mitosis regulation.