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KMID : 0624620150480080473
BMB Reports
2015 Volume.48 No. 8 p.473 ~ p.478
An inhibitory role of NEK6 in TGF¥â/Smad signaling pathway
Zuo Jie

Ma Haijie
Cai Hao
Wu Yanhua
Jiang Wei
Yu Long
Abstract
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.
KEYWORD
NEK6, Nuclear translocation, Smad4, TGF¥â, Transcription
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