Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway

Fei Chen, Zhuo Zhang, Jacquelyn Bower, Yongju Lu, Stephen S. Leonard, Min Ding, Vince Castranova, Helen Piwnica-Worms, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Arsenite is a known human carcinogen that induces tumorigenesis through either a genotoxic or an epigenetic mechanism. In this study, the effect of arsenite on cell cycle regulation and the mechanisms that contribute to this effect were investigated. Treatment of the cells with arsenite suppressed cell proliferation and reduced cell viability in a dose- or time-dependent manner. Analysis of cell cycle profile and cell cycle regulatory proteins indicated that arsenite arrested the cell cycle at G2/M phase, partially through induction of cell division cycle 25 (Cdc25) isoform C (Cdc25C) degradation via ubiquitin-proteasome pathways. Mutation of the putative KEN box within the region 151 to 157 of human Cdc25C or treatment of the cells with a peptide competitor encompassing the KEN box partially inhibited arsenite-induced ubiquitination of Cdc25C. Thus, these results indicate that the regulated ubiquitination of Cdc25C may be involved in the arsenite-induced proteolytic down-regulation of Cdc25C activity in the G2/M phase of the cell cycle and suggest a link between cell cycle and the carcinogenic effects of arsenite.

Original languageEnglish
Pages (from-to)1990-1995
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number4
DOIs
StatePublished - Feb 19 2002

ASJC Scopus subject areas

  • General

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