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Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells.

Authors
Zhang-P; Gao-W; Li-H; Reed-E; Chen-F
Source
Biochem Biophys Res Commun 2005 Mar; 328(2):567-572
NIOSHTIC No.
20025961
Abstract
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.
Keywords
Cancer; Mutagenesis; Gene-mutation; Genetics; DNA-damage; Chk2-kinase; Degradation; Ubiquitination; Cisplatin-resistance
Contact
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505
CODEN
BBRCA9
CAS No.
15663-27-1
Publication Date
20050311
Document Type
Journal Article
Email Address
lfd3@cdc.gov
Fiscal Year
2005
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0006-291X
NIOSH Division
HELD
Source Name
Biochemical and Biophysical Research Communications
State
WV
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