Arsenite-Induced Cdc25C Degradation Is Through the KEN-Box and Ubiquitin-Proteasome Pathway

Details

• Personal Author:
  Bower J ; Castranova, Vincent ; Chen F ; Ding M ; Leonard, Stephen S. ; Lu Y ; Piwnica-Worms H ; Shi X ; Zhang Z
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Arsenic Carcinogens Cardiovascular Diseases Cardiovascular System Dermatitis Environmental Exposure Inorganic Chemicals Kidney Diseases Liver Lung Lung Diseases Neoplasms Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety Skin Skin Diseases Urogenital Diseases Urogenital System

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• Keywords:
  Arsenic-compounds Arsenites Bladder-cancer Cardiovascular-system-disorders Dermatosis Environmental-exposure Genotoxic-effects Humans Kidney-disorders Liver-cancer Lung-cancer Occupational-exposure Peptides Proteins Skin-cancer Tumorigenesis

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• ISSN:
  1091-6490
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Missouri ; OSHA Region 3 ; OSHA Region 7 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  99
• Issue:
  4
• NIOSHTIC Number:
  nn:20023001
• Citation:
  Proc Natl Acad Sci USA 2002 Feb; 99(4):1990-1995
• Contact Point Address:
  Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  lfd3@cdc.gov
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2)
• Editor(s):
  Kirschner MW
• Federal Fiscal Year:
  2002
• Peer Reviewed:
  True
• Source Full Name:
  Proceedings of the National Academy of Sciences of the United States of America
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f9f28af1ffc39db3f453c7985cf521168785a4f1ee73d7ac1d492bad918546cc301751aafd4b9d056cefac8617bef6e442d0e0aa5d0b761713019c3f685b7cb1
• Download URL:
  https://stacks.cdc.gov/view/cdc/199596/cdc_199596_DS1.pdf
• File Type:
  [PDF - 262.12 KB ]