Deubiquitinase USP13 Maintains Glioblastoma Stem Cells by Antagonizing FBXL14-mediated Myc Ubiquitination

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2016 Dec 8

PMID 27923907

Citations 85

Authors

Xiaoguang Fang

Wenchao Zhou

Qiulian Wu

Zhi Huang

Yu Shi

Kailin Yang

Cong Chen

Qi Xie

Stephen C Mack

Xiuxing Wang

Angel M Carcaboso

Andrew E Sloan

Gaoliang Ouyang

Roger E McLendon

Xiu-Wu Bian

Jeremy N Rich

Shideng Bao

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is the most lethal brain tumor and harbors glioma stem cells (GSCs) with potent tumorigenic capacity. The function of GSCs in tumor propagation is maintained by several core transcriptional regulators including c-Myc. c-Myc protein is tightly regulated by posttranslational modification. However, the posttranslational regulatory mechanisms for c-Myc in GSCs have not been defined. In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation. In contrast, overexpression of the ubiquitin E3 ligase FBXL14 induced c-Myc degradation, promoted GSC differentiation, and inhibited tumor growth. Ectopic expression of the ubiquitin-insensitive mutant T58A-c-Myc rescued the effects caused by FBXL14 overexpression or USP13 disruption. These data suggest that USP13 and FBXL14 play opposing roles in the regulation of GSCs through reversible ubiquitination of c-Myc.

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