Cisplatin induces p53-dependent FLICE-like inhibitory protein ubiquitination in ovarian cancer cells

被引：70

作者：

Abedini, Mohammad R. ^{[4
,5
]}

Muller, Emilie J. ^{[2
,5
]}

Brun, Jan ^{[3
,9
]}

Bergeron, Richard ^{[2
,5
,8
]}

Gray, Douglas A. ^{[3
,7
,9
]}

Tsang, Benjamin K. ^{[1
,5
,6
]}

机构：

[1] Ottawa Hlth Res Inst, Dept Chron Dis, Ottawa, ON K1Y 4E9, Canada

[2] Ottawa Hlth Res Inst, Dept Neurosci, Ottawa, ON K1Y 4E9, Canada

[3] Ottawa Hlth Res Inst, Canc Therapeut Programs, Ottawa, ON K1Y 4E9, Canada

[4] Birjand Univ Med Sci, Dept Phys & Pharmacol, Birjand, Iran

[5] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1N 6N5, Canada

[6] Univ Ottawa, Dept Obstet & Gynaecol, Ottawa, ON K1N 6N5, Canada

[7] Univ Ottawa, Dept Med, Ottawa, ON K1N 6N5, Canada

[8] Univ Ottawa, Dept Psychiat, Ottawa, ON K1N 6N5, Canada

[9] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada

来源：

CANCER RESEARCH | 2008年 / 68卷 / 12期

关键词：

D O I：

10.1158/0008-5472.CAN-08-0673

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

收藏

页码：4511 / 4517

页数：7

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