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

Area of Science:

• Molecular Biology
• Cancer Biology
• Cell Cycle Regulation

Background:

• NEK2 (NIMA-related kinase 2) is a serine/threonine kinase crucial for cell cycle progression, specifically centrosome splitting and chromosome segregation.
• Aberrant NEK2 expression in cancer is linked to centrosome cycle dysregulation and aneuploidy, highlighting its oncogenic potential.

Purpose of the Study:

• To investigate the novel role of NEK2 in nuclear functions beyond its known role in cell division.
• To explore the potential involvement of NEK2 in RNA splicing processes within cancer cells.

Main Methods:

• Immunofluorescence microscopy to determine NEK2 localization in cancer cells.
• Co-immunoprecipitation assays to identify NEK2 interacting partners.
• In vitro kinase assays and reporter minigene assays to assess NEK2's effect on splicing factors and activity.
• Western blotting and RT-qPCR to analyze protein phosphorylation and gene expression changes.

Main Results:

• NEK2 was found to localize in the nucleus of various cancer cells, co-localizing with splicing factors SRSF1 and SRSF2.
• NEK2 directly interacts with and phosphorylates splicing factors, including the oncoprotein SRSF1.
• NEK2 overexpression altered SRSF1 splicing activity, while NEK2 knockdown mimicked SRSF1 knockdown effects, inducing pro-apoptotic variants and sensitizing cells to apoptosis.

Conclusions:

• NEK2 functions as a novel splicing factor kinase, implicating it in the regulation of alternative splicing.
• NEK2's oncogenic activity may be partly attributed to its modulation of alternative splicing, a critical process frequently altered in cancer.
• Targeting NEK2 could offer a dual therapeutic strategy by affecting both cell division and aberrant splicing in cancer.