KMID : 0624620150480080473
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BMB Reports 2015 Volume.48 No. 8 p.473 ~ p.478
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An inhibitory role of NEK6 in TGF¥â/Smad signaling pathway
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Zuo Jie
Ma Haijie Cai Hao Wu Yanhua Jiang Wei Yu Long
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Abstract
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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 (TGF¥â) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGF¥â- mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGF¥â. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGF¥â function. Moreover, we identified that NEK6 could be regulated by TGF¥â and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGF¥â/Smad pathway and tum-origenesis.
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KEYWORD
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NEK6, Nuclear translocation, Smad4, TGF¥â, Transcription
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