Nek11, a new member of the NIMA family of kinases, involved in DNA replication and genotoxic stress responses

Kohji Noguchi, Hidesuke Fukazawa, Yuko Murakami, Yoshimasa Uehara

研究成果: Article査読

55 被引用数 (Scopus)

抄録

DNA replication and genotoxic stresses activate various checkpoint-associated protein kinases, and check-point dysfunction often leads to cell lethality. Here, we have identified new members of the mammalian NIMA family of kinases, termed Nek11L and Nek11S (NIMAJ-related kinase 11 Long and Short isoform) as novel DNA replication/damage stresses-responsive kinases. Molecular cloning and biochemical studies showed that the catalytic domain of Nek11 is most similar to Nek4 and Nek3, and substrate specificity of Nek11L is distinguishable from those of NIMA and Nek2. The expression of nek11L mRNA increased through S to G2/M phase, and subcellular localization of Nek11 protein altered between interphase and prometaphase, suggesting multiple roles of Nek11. We found an activation of Nek11 kinase activity when cells were treated with various DNA-damaging agents and replication inhibitors, and this activation of Nek11 was suppressed by caffeine in HeLaS3 cells. The transient expression of wild-type Nek11L enhanced the aphidicolin-induced S-phase arrest, whereas the aphidicolin-induced S-phase arrest was reduced in the U2OS cell lines expressing kinase-negative NekllL (K61R), and these cells were more sensitive to aphidicolin-induced cell lethality. Collectively, these results suggest that Nek11 has a role in the S-phase checkpoint downstream of the caffeine-sensitive pathway.

本文言語English
ページ(範囲)39655-39665
ページ数11
ジャーナルJournal of Biological Chemistry
277
42
DOI
出版ステータスPublished - 2002 10月 18

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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