Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis

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• 作者：Zhuan Zhou^a ; ^b ; ¹ ; Aiping Luo^c ; ¹ ; Indira Shrivastava^d ; ¹ ; Mingjing He^a ; ^e ; Yi Huang^b ; Ivet Bahar^d ; Zhihua Liu^c ; ^{liuzh@cicams.ac.cn} ; Yong Wan^a ; ^b ; ^{yow4@pitt.edu}
• 关键词：USP11 ; XIAP ; Apoptosis ; Tumorigenesis
• 刊名：EBioMedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：Complete
• 页码：48-61
• 全文大小：2946 K
• 卷排序：15

文摘

Identification of USP11 as a pivotal player in promoting tumorigenesis via a non-biased screening of deubiquitinase library. Identification of XIAP as a substrate for USP11 using a TAP-protein complex purification coupled with mass spectrometry. Stabilization of XIAP by USP11 leads to inhibition of anoikis and apoptosis that in turn promotes tumor cell survival.Targeting ubiquitin-proteasome pathway becomes an emerging strategy to develop anti-cancer treatment. The impact of deubiquitinase in counteracting ubiquitylation and regulating tumorigenesis has recently drawn our attention. To systematically evaluate the role of deubiquitinases in human genome in regulating mammary tumorigenesis, we have conducted a non-biased screening of deubiquitinases library with examination of individual deubiquitinase in predisposing normal mammary gland cell into cancer cell. Our endeavor leads to identification of USP11 as a pivotal player that promotes mammary tumor formation. Our molecular characterization has further revealed that stabilization of XIAP by USP11 results in the inhibition of cancer cell death thereby promoting tumorigenesis.