E3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production.

Autor: Chen L; Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Key Laboratory of Urological Diseases, Wuhan, China.; Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Wuhan, China.; Institute of Urology, Wuhan University, Wuhan, China.; Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Wuhan, China.; Wuhan Clinical Research Center for Urogenital Tumors, Wuhan, China., Hu X; Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China., Wang G; Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China., Yu F; Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China., Dai Z; Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, China., Jian X; Department of Pathology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China., Li Y; Department of Urology, Jinning District People's Hospital, Kunming, China. liyongstudent@126.com., Xiang W; Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China. xiangwan@whu.edu.cn., Meng Z; Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. mengzhe@whu.edu.cn.; Hubei Key Laboratory of Urological Diseases, Wuhan, China. mengzhe@whu.edu.cn.; Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Wuhan, China. mengzhe@whu.edu.cn.; Institute of Urology, Wuhan University, Wuhan, China. mengzhe@whu.edu.cn.; Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Wuhan, China. mengzhe@whu.edu.cn.; Wuhan Clinical Research Center for Urogenital Tumors, Wuhan, China. mengzhe@whu.edu.cn.; Department of Urology, Daye Hospital of Traditional Chinese Medicine, Huangshi, China. mengzhe@whu.edu.cn.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Dec 27; Vol. 82 (1), pp. 27. Date of Electronic Publication: 2024 Dec 27.
DOI: 10.1007/s00018-024-05545-0
Abstrakt: Aldosterone-producing adenoma (APA) is a leading cause of primary aldosteronism (PA), a condition marked by excessive aldosterone secretion. CYP11B2, the aldosterone synthase, plays a critical role in aldosterone biosynthesis and the development of APA. Despite its significance, encoding regulatory mechanisms governing CYP11B2, particularly its degradation, remain poorly understood. In this study, we sought to uncover novel regulators of CYP11B2 stability by conducting a siRNA screen targeting E3 ubiquitin ligases. Our results identified TRIM2 as a key negative regulator of CYP11B2, where its overexpression led to a significant reduction in CYP11B2 protein levels and a concomitant decrease in aldosterone production in adrenal tumor cells. Mechanistically, we demonstrated that TRIM2 interacts with CYP11B2 via its RBCC domain, promoting K29/48-linked polyubiquitination and destabilization of CYP11B2. Further results revealed that TRIM2 is downregulated in APA tissues, showing differential expression between the zona glomerulosa (ZG) and zona fasciculata (ZF) of normal adrenal tissue. These findings highlight TRIM2 as a novel modulator of aldosterone synthesis through CYP11B2 degradation, offering a potential therapeutic target for APA.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: 2020014), and All patients had signed the informed consents before the study. Consent for publication: All the authors agree with the publication of the manuscript. Conflict of interest: The authors declare that there is no conflict of interests
(© 2024. The Author(s).)
Databáze: MEDLINE
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