title: Nek6 overexpression antagonizes p53-induced senescence in human cancer cells.
abstract: Nek6 is an NIMA-related kinase that plays a critical role in mitotic cell cycle progression. Recent studies have shown that Nek6 is upregulated in various human cancers, but the function of Nek6 in tumorigenesis is largely unknown. Here, we examined the role of Nek6 in cellular senescence. Our data revealed that Nek6 expression is decreased both in both the replicative senescence of human normal fibroblasts and premature senescence induced by p53 expression in EJ human bladder cancer cells and H1299 human lung cancer cells. Interestingly, the enforced expression of Nek6 in EJ and H1299 cells completely suppresses p53-induced senescence, whereas the expression of kinase-dead Nek6 did not affect p53-induced senescence. Mechanistic studies revealed that cell cycle arrest in the G1 and G2/M phases, as well as the reduction of cyclin B and cdc2 protein level upon p53 expression were significantly reduced by Nek6 overexpression. In addition, p53-induced increases in intracellular levels of ROS were also inhibited in cells overexpressing Nek6. These results suggest that the downregulation of Nek6 expression is required for the onset of p53-induced cellular senescence and imply a possible role of Nek6 in tumorigenesis.
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jee
authors.forename: Ae Jeong
authors.initials: AJ
authors.lastname: Kim
authors.forename: Naree
authors.initials: N
authors.lastname: Song
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Minjee
authors.initials: M
authors.lastname: Kim
authors.forename: Hyongjong
authors.initials: H
authors.lastname: Koh
authors.forename: Jeanho
authors.initials: J
authors.lastname: Yun
mesh_terms: D016203:CDC2 Protein Kinase; D002455:Cell Division; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D000072379:NIMA-Related Kinases; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C459456:NEK6 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases