Even Yasmine, Escande Marie-Line, Fayet Claire, Genevière Anne-Marie
Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins (BIOM), Observatoire Océanologique, F-66650, Banyuls/Mer, France.
PLoS One. 2016 Feb 17;11(2):e0149184. doi: 10.1371/journal.pone.0149184. eCollection 2016.
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.
核仁周围区(PNC)是一种主要在癌细胞中形成的亚核结构;其出现率与转移能力呈正相关。尽管已经在PNC中鉴定出几种RNA结合蛋白,但该区域的分子功能仍不清楚。在这里,我们证明细胞周期蛋白依赖性激酶13(CDK13)是PNC新发现的组成成分。CDK13是一种参与基因表达调控的激酶,其过表达被发现会改变前体mRNA加工过程。在本研究中,我们表明CDK13在PNC中富集,并在整个细胞周期中与PNC成分PTB共定位。相反,已知与CDK13相关的细胞周期蛋白K和L以及潜在的激酶底物都不会在PNC中积累。我们进一步表明,CDK13的过表达会增加PNC的出现率,这表明CDK13可能是PNC形成的决定因素。这一结果与CDK13基因在不同类型癌症中扩增的发现相关,表明这种激酶可能在人类癌症发展中起作用。