PDF(Pubmed)
Abstract：
PCTAIRE1 (also known as CDK16) is a serine-threonine kinase implicated in physiological processes like neuronal development, vesicle trafficking, spermatogenesis and cell proliferation. However, its exact role in cell division remains unclear. In this study, using a library screening approach, we identified PCTAIRE1 among several candidates that resisted mitotic arrest and mitotic cell death induced by polyomavirus small T (PolST) expression in mammalian cells. Our study showed that PCTAIRE1 is a mitotic kinase that localizes at centrosomes during G2 and at spindle poles as the cells enter mitosis, and then at the midbody during cytokinesis. We also report that PCTAIRE1 protein levels fluctuate through the cell cycle and reach their peak at mitosis, during which there is an increase in PCTAIRE1 phosphorylation as well. Interestingly, knockdown of PCTAIRE1 resulted in aberrant mitosis by interfering with spindle assembly and chromosome segregation. Further, we found that PCTAIRE1 promotes resistance of cancer cells to antimitotic drugs, and this underscores the significance of PCTAIRE1 as a potential drug target for overcoming chemotherapeutic resistance. Taken together, these studies establish PCTAIRE1 as a critical mediator of mitotic progression and highlight its role in chemotherapeutic resistance. This article has an associated First Person interview with the first author of the paper.
摘要：
PCTAIRE1（也称为CDK16）是一种丝氨酸-苏氨酸激酶，参与神经元发育等生理过程。囊泡贩运，精子发生和细胞增殖。然而,其在细胞分裂中的确切作用尚不清楚。在这项研究中,使用图书馆筛选方法，我们发现PCTAIRE1可以抵抗哺乳动物细胞中多瘤病毒小T(PolST)表达诱导的有丝分裂阻滞和有丝分裂细胞死亡.我们的研究表明，PCTAIRE1是一种有丝分裂激酶，在G2期间定位于中心体，在细胞进入有丝分裂时位于纺锤体极，然后在胞质分裂期间在中体。我们还报道了PCTAIRE1蛋白水平在细胞周期中波动，并在有丝分裂时达到峰值，在此期间PCTAIRE1磷酸化也增加。有趣的是,PCTAIRE1的敲低通过干扰纺锤体组装和染色体分离导致异常有丝分裂。Further,我们发现PCTAIRE1促进癌细胞对抗有丝分裂药物的抗性，这强调了PCTAIRE1作为克服化疗耐药的潜在药物靶点的重要性。一起来看,这些研究将PCTAIRE1确立为有丝分裂进展的关键介质,并强调了其在化疗耐药中的作用.本文与该论文的第一作者进行了相关的第一人称访谈。
