Oncotarget

Research Papers:

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 and Ho-Geun Yoon

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Oncotarget. 2016; 7:41110-41122. https://doi.org/10.18632/oncotarget.9002

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Abstract

Soo-Yeon Park1,*, Younghwa Na2,*, Mee-Hee Lee1,*, Jae-Sung Seo1, Yoo-Hyun Lee3, Kyung-Chul Choi4, Hyo-Kyoung Choi5, Ho-Geun Yoon1

1Department of Biochemistry and Molecular Biology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seodaemun-gu, Seoul, South Korea

2College of Pharmacy, CHA University, Gyeonggi-do, Pocheon, South Korea

3Department of Food Science and Nutrition, The University of Suwon, Kyunggi-do, South Korea

4Department of Biomedical Sciences, University of Ulsan College of Medicine, Poongnap-dong, Songpa-gu, Seoul, South Korea

5Division of Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do, South Korea

*These authors contributed equally to this work

Correspondence to:

Kyung-Chul Choi, email: choikc75@amc.seoul.kr

Hyo-Kyoung Choi, email: chkyoung@kfri.re.kr

Ho-Geun Yoon, email: yhgeun@yuhs.ac

Keywords: SUMOylation, TBL1, TBLR1, NF-κB, inflammation

Received: October 29, 2015     Accepted: March 29, 2016     Published: April 26, 2016

ABSTRACT

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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