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SUMOylation of TBL1 and TBLR1 promotes androgen-independent prostate cancer cell growth.

 Soo-Yeon Park  ;  Younghwa Na  ;  Mee-Hee Lee  ;  Jae-Sung Seo  ;  Yoo-Hyun Lee  ;  Kyung-Chul Choi  ;  Hyo-Kyoung Choi  ;  Ho-Geun Yoon 
 ONCOTARGET , Vol.7(27) : 41110-41122, 2016 
Journal Title
Issue Date
Androgens/pharmacology ; Cell Line, Tumor ; Cell Proliferation*/drug effects ; Cytokines/metabolism ; Humans ; Inflammation Mediators/metabolism ; Male ; Nuclear Proteins/metabolism* ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Repressor Proteins/metabolism* ; Sumoylation* ; Transducin/metabolism*
NF-κB ; SUMOylation ; TBL1 ; TBLR1 ; inflammation
Chronic inflammation is strongly associated with prostate cancer pathogenesis. Transducin β-like protein (TBL1) and Transducin β-like 1X-linked receptor 1 (TBLR1) have been identified recently as a coactivator for NF-κB-mediated transcription; however, the underlying mechanism by which TBL1 and TBLR1 activate NF-κB function during inflammation remains unknown. Here, we demonstrate that cytokine production is significantly elevated in androgen-independent PC-3 prostate cancer cells compared with androgen-dependent LNCaP prostate cancer cells. Elevated cytokine production positively correlates with the TBL1 and TBLR1 SUMOylation level in PC-3 cells. We show that both TBL1 and TBLR1 are SUMOylated in response to TNF-α treatment, and this increases formation of the TBL1-TBLR1-NF-κB complex, which leads to NF-κB-mediated transcriptional activation of cytokine gene expression. Conversely, SENP1-mediated deSUMOylation of TBL1 and TBLR1 inhibits NF-κB-target gene expression by dissociating TBL1 and TBLR1 from the nuclear hormone receptor corepressor (NCoR) complex. TBL1 knockdown substantially suppresses inflammatory signaling and PC-3 cell proliferation. Collectively, these results suggest that targeted SUMOylation of TBL1 and TBLR1 may be a useful strategy for therapeutic treatment of androgen-independent prostate cancer.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
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