An inhibitory role of NEK6 in TGFbeta/Smad signaling pathway

An inhibitory role of NEK6 in TGFbeta/Smad signaling pathway

The NEK6 (NIMA-related kinases 6) is reported to play po-tential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key me...

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Veröffentlicht in:BMB reports 2015-08, Vol.48 (8)
Hauptverfasser: Zuo, J., Fudan University, Shanghai, China, Ma, H., Zhoushan Hospital, Zhejiang, China, Cai, H., Fudan University, Shanghai, China, Wu, Y., Fudan University, Shanghai, China, Jiang, W., Fudan University, Shanghai, China, Yu, L., Fudan University, Shanghai, China
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Sprache:eng
Schlagworte:
NEK6,Nuclear translocation,Smad4,TGFbeta
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Zusammenfassung:The NEK6 (NIMA-related kinases 6) is reported to play po-tential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key member of transforming growth factor beta (TGFbeta) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFbeta-betamediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFbeta. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGF ƒÒ function. Moreover, we identified that NEK6 could be regulated by TGFbeta and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFbeta/Smad pathway and tum-origenesis
ISSN:1976-6696