title: Ubiquitin-specific protease 11 (USP11) functions as a tumor suppressor through deubiquitinating and stabilizing VGLL4 protein.
abstract: VGLL4 is a transcriptional repressor that interacts with transcription factors TEADs and inhibits YAP-induced overgrowth and tumorigenesis. VGLL4 protein was dramatically reduced in various types of human cancers. But how VGLL4 protein is post-transcriptional regulated is poorly understood. In this study, we identify deubiquitinating enzyme USP11 as a novel VGLL4 interactor. We reveal that the USP domain of USP11 and the N-terminal region of VGLL4 are required for mutual binding. USP11 controls VGLL4 protein stability by promoting its deubiquitination. Furthermore, our results show that knockdown of USP11 promotes cell growth, migration, and invasion in a YAP-dependent manner. Together, our results suggest that USP11 may exert its tumor suppressor role by modulating VGLL4/YAP-TEADs regulatory loop.
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Encheng
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, P. R. China.
authors.forename: Pingzhao
authors.initials: P
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai, P. R. China.
authors.forename: Chenji
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University Shanghai, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
keywords: Hippo pathway; TEADs; USP11; VGLL4; deubiquitination