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Cancer Research 68, 4511, June 15, 2008. doi: 10.1158/0008-5472.CAN-08-0673
© 2008 American Association for Cancer Research
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Priority Reports

Cisplatin Induces p53-Dependent FLICE-Like Inhibitory Protein Ubiquitination in Ovarian Cancer Cells

Mohammad R. Abedini1,9, Emilie J. Muller1,7, Jan Brun5,8, Richard Bergeron1,4,7, Douglas A. Gray3,5,8 and Benjamin K. Tsang1,2,6

Departments of 1 Cellular and Molecular Medicine, 2 Obstetrics and Gynaecology, 3 Medicine, 4 Psychiatry, and 5 Biochemistry, Microbiology and Immunology, University of Ottawa; 6 Chronic Disease, 7 Neuroscience, and 8 Cancer Therapeutics Programs, Ottawa Health Research Institute, Ottawa, Ontario, Canada; and 9 Department of Physiology and Pharmacology, Birjand University of Medical Sciences, Birjand, Iran

Requests for reprints: Benjamin K. Tsang, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9. Phone: 613-798-5555, ext. 16040; Fax: 613-761-4403; E-mail: btsang{at}ohri.ca.

Key Words: FLIP • p53 • CDDP • Itch • ubiquitin-proteasome pathway • chemoresistance • ovarian cancer

Understanding the mechanism of cisplatin (CDDP) action may improve therapeutic strategy for ovarian cancer. Although p53 and FLICE-like inhibitory protein (FLIP) are determinants of CDDP sensitivity in ovarian cancer, the interaction between p53 and FLIP remains poorly understood. Here, using two chemosensitive ovarian cancer cell lines and various molecular and cellular approaches, we show that CDDP induces p53-dependent FLIP ubiquitination and degradation, and apoptosis in vitro. Moreover, we showed that Itch (an E3 ligase) forms a complex with FLIP and p53 upon CDDP treatment. These results suggest that p53 facilitates FLIP down-regulation by CDDP-induced FLIP ubiquitination and proteasomal degradation. [Cancer Res 2008;68(12):4511–7]




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[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.