Inducible Degradation of Checkpoint Kinase 2 Links to Cisplatin-Induced Resistance in Ovarian Cancer Cells

Details

• Personal Author:
  Chen F ; Gao W ; Li H ; Reed E ; Zhang P
• Description:
  Checkpoint kinase 2 (Chk2) is one of the critical kinases governing the cell cycle checkpoint, DNA damage repair, and cell apoptosis in response to DNA damaging signals. In the present report, we demonstrate that Chk2 kinase is degraded at the protein level in response to cisplatin through ubiquitin - proteasome pathway. This degradation was independent of the Thr68 phosphorylation, ATM kinase, and BRCA1 tumor suppressor. Examination of Chk2 protein revealed a decreased expression of Chk2 protein in cisplatin-resistant ovarian cancer cell lines, suggesting that degradation or decreased expression of Chk2 is partially responsible for chemo-resistance. Site-directed mutation of the putative destruction box in the Chk2 protein did not affect the Chk2 degradation induced by cisplatin. Therefore, these results are the first to indicate a novel mechanism of regulating Chk2 in cisplatin-induced resistance of cancer cells. [Description provided by NIOSH]
• Subjects:
  DNA Genetics Mutagens Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Chk2 Kinase Cancer Chk2-kinase Cisplatin-resistance Cisplatin Resistance Degradation DNA-damage Gene-mutation Mutagenesis Ubiquitination
• ISSN:
  0006-291X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  328
• Issue:
  2
• NIOSHTIC Number:
  nn:20025961
• Citation:
  Biochem Biophys Res Commun 2005 Mar; 328(2):567-572
• Contact Point Address:
  Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
• Email:
  lfd3@cdc.gov
• CAS Registry Number:
  Cisplatin (CAS RN 15663-27-1)
• Federal Fiscal Year:
  2005
• Peer Reviewed:
  True
• Source Full Name:
  Biochemical and Biophysical Research Communications
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eafa2419473bcb183d065be854436cdd4470dc4ba4832a4c1eea1d567d991208f007e741bed24699ff663fbc96ee5b86428c7dc075146bebaf5bb8b093dfaa3c
• Download URL:
  https://stacks.cdc.gov/view/cdc/197116/cdc_197116_DS1.pdf
• File Type:
  [PDF - 482.34 KB ]