The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival.
The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival.
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DOI：
10.1093/nar/gkt1307
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发表时间：
2014-03
影响因子：
14.9
通讯作者：
Sette C
中科院分区：
文献类型：
--
作者：
Naro C;Barbagallo F;Chieffi P;Bourgeois CF;Paronetto MP;Sette C
NEK2是一种丝氨酸/苏氨酸激酶，通过特定底物的磷酸化，在细胞周期的G2/M期促进中心体分裂并确保正确的染色体分离。NEK2在癌细胞中的异常表达和活性导致中心体周期失调和非整倍体。因此，在细胞周期进程中需要严格调节NEK2的功能。在这项研究中，我们发现NEK2定位于来自几种组织的癌细胞的细胞核中。特别是，NEK2与SRSF1和SRSF2在剪接斑点中共定位。此外，NEK2与几个剪接因子相互作用，并使其中一些剪接因子磷酸化，包括致癌的SRSF1蛋白。NEK2的过表达诱导内源性SR蛋白磷酸化，并影响SRSF1对报告基因和内源性靶标的剪接活性，而不依赖于SRPK1。相反，像SRSF1一样，NEK2的敲低会诱导SRSF1靶基因的促凋亡变异体的表达，并使细胞对凋亡敏感。我们的研究结果确定NEK2是一种新的剪接因子激酶，并表明其部分致癌活性可能归因于其调节选择性剪接的能力，这是癌细胞中经常改变的基因表达调控的关键步骤。
NEK2 is a serine/threonine kinase that promotes centrosome splitting and ensures correct chromosome segregation during the G2/M phase of the cell cycle, through phosphorylation of specific substrates. Aberrant expression and activity of NEK2 in cancer cells lead to dysregulation of the centrosome cycle and aneuploidy. Thus, a tight regulation of NEK2 function is needed during cell cycle progression. In this study, we found that NEK2 localizes in the nucleus of cancer cells derived from several tissues. In particular, NEK2 co-localizes in splicing speckles with SRSF1 and SRSF2. Moreover, NEK2 interacts with several splicing factors and phosphorylates some of them, including the oncogenic SRSF1 protein. Overexpression of NEK2 induces phosphorylation of endogenous SR proteins and affects the splicing activity of SRSF1 toward reporter minigenes and endogenous targets, independently of SRPK1. Conversely, knockdown of NEK2, like that of SRSF1, induces expression of pro-apoptotic variants from SRSF1-target genes and sensitizes cells to apoptosis. Our results identify NEK2 as a novel splicing factor kinase and suggest that part of its oncogenic activity may be ascribed to its ability to modulate alternative splicing, a key step in gene expression regulation that is frequently altered in cancer cells.
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影响因子：
16
作者：
Lin, SR;Xiao, R;Fu, XD
通讯作者：
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通讯作者：
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通讯作者：
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