The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival

Chiara Naro, Federica Barbagallo, Paolo Chieffi, Cyril F. Bourgeois, Maria Paola Paronetto, Claudio Sette

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3218-3227
Number of pages10
JournalNucleic Acids Research
Volume42
Issue number5
DOIs
Publication statusPublished - 2014

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Cell Survival
Centrosome
Phosphotransferases
Cell Cycle
Phosphorylation
Protein Splicing
Neoplasms
Chromosome Segregation
G2 Phase
Protein-Serine-Threonine Kinases
Alternative Splicing
Gene Expression Regulation
Aneuploidy
Cell Nucleus
Cell Division
Apoptosis
Genes
RNA Splicing Factors
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival. / Naro, Chiara; Barbagallo, Federica; Chieffi, Paolo; Bourgeois, Cyril F.; Paronetto, Maria Paola; Sette, Claudio.

In: Nucleic Acids Research, Vol. 42, No. 5, 2014, p. 3218-3227.

Research output: Contribution to journalArticle

Naro, Chiara ; Barbagallo, Federica ; Chieffi, Paolo ; Bourgeois, Cyril F. ; Paronetto, Maria Paola ; Sette, Claudio. / The centrosomal kinase NEK2 is a novel splicing factor kinase involved in cell survival. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 5. pp. 3218-3227.
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