title: An inhibitory role of NEK6 in TGFβ/Smad signaling pathway.
abstract: The NEK6 (NIMA-related kinases 6) is reported to play potential 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 (TGFβ) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFβ-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFβ. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGFβ function. Moreover, we identified that NEK6 could be regulated by TGFβ and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFβ/Smad pathway and tumorigenesis.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zuo
authors.affiliation: Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
authors.forename: Haijie
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D000072379:NIMA-Related Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases