Oxidative stress-induced cyclin D1 depletion and its role in cell cycle processing

Chul Woong Pyo, Joon Hwan Choi, Sang Muk Oh, Sang Yun Choi

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background Cyclin D1 is immediately down-regulated in response to reactive oxygen species (ROS) and implicated in the induction of cell cycle arrest in G2 phase by an unknown mechanism. Either treatment with a protease inhibitor alone or expression of protease-resistant cyclin D1 T286A resulted in only a partial relief from the ROS-induced cell cycle arrest, indicating the presence of an additional control mechanism. Methods Cells were exposed to hydrogen peroxide (H2O2), and analyzed to assess the changes in cyclin D1 level and its effects on cell cycle processing by kinase assay, de novo synthesis, gene silencing, and polysomal analysis, etc. Results Exposure of cells to excessive H2O2 induced ubiquitin-dependent proteasomal degradation of cyclin D1, which was subsequently followed by translational repression. This dual control mechanism was found to contribute to the induction of cell cycle arrest in G2 phase under oxidative stress. Silencing of an eIF2α kinase PERK significantly retarded cyclin D1 depletion, and contributed largely to rescuing cells from G2 arrest. Also the cyclin D1 level was found to be correlated with Chk1 activity. Conlclusions In addition to an immediate removal of the pre-existing cyclin D1 under oxidative stress, the following translational repression appear to be required for ensuring full depletion of cyclin D1 and cell cycle arrest. Oxidative stress-induced cyclin D1 depletion is linked to the regulation of G2/M transit via the Chk1-Cdc2 DNA damage checkpoint pathway. General significance The control of cyclin D1 is a gate keeping program to protect cells from severe oxidative damages.

Original languageEnglish
Pages (from-to)5316-5325
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1830
Issue number11
DOIs
Publication statusPublished - 2013

Keywords

  • Cell cycle
  • Chk1
  • Oxidative stress
  • Proteolysis
  • Translational repression

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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