CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment.

CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment.
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DOI:
10.1371/journal.pone.0149184
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Genevière AM
Genevière AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Even Y;Escande ML;Fayet C;Genevière AM

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核仁周围区室(PNC)是主要在癌细胞中形成的亚核结构;其患病率与转移能力呈正相关。虽然几种RNA结合蛋白已在PNC的特点,这个隔间的分子功能仍然不清楚。在这里,我们证明,细胞周期蛋白依赖性激酶13(CDK 13)是一个新发现的成分PNC。CDK 13是一种参与基因表达调节的激酶,其过表达被发现改变前mRNA加工。在这项研究中,我们表明,CDK 13是富集在PNC和共定位所有沿着细胞周期与PNC组件PTB。相反,既不是周期蛋白K和L,已知与CDK 13,也不是潜在的激酶底物积累在PNC。我们进一步表明,CDK 13过表达增加PNC患病率,表明CDK 13可能是PNC形成的决定因素。这一结果与CDK 13基因在不同类型癌症中扩增的发现有关,表明这种激酶可能有助于人类癌症的发展。
The perinucleolar compartment (PNC) is a subnuclear stucture forming predominantly in cancer cells; its prevalence positively correlates with metastatic capacity. Although several RNA-binding proteins have been characterized in PNC, the molecular function of this compartment remains unclear. Here we demonstrate that the cyclin–dependent kinase 13 (CDK13) is a newly identified constituent of PNC. CDK13 is a kinase involved in the regulation of gene expression and whose overexpression was found to alter pre-mRNA processing. In this study we show that CDK13 is enriched in PNC and co-localizes all along the cell cycle with the PNC component PTB. In contrast, neither the cyclins K and L, known to associate with CDK13, nor the potential kinase substrates accumulate in PNC. We further show that CDK13 overexpression increases PNC prevalence suggesting that CDK13 may be determinant for PNC formation. This result linked to the finding that CDK13 gene is amplified in different types of cancer indicate that this kinase can contribute to cancer development in human.