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

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Foilsithe in:Cellular and Molecular Life Sciences vol. 82, no. 1 (Dec 2025), p. 27
Foilsithe / Cruthaithe:
Springer Nature B.V.
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Rochtain ar líne:Citation/Abstract
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022 |a 1420-682X 
022 |a 1420-9071 
022 |a 0014-4754 
024 7 |a 10.1007/s00018-024-05545-0  |2 doi 
035 |a 3149308699 
045 2 |b d20251201  |b d20251231 
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245 1 |a E3 ubiquitin ligase TRIM2 identified as a novel suppressor of CYP11B2 and aldosterone production 
260 |b Springer Nature B.V.  |c Dec 2025 
513 |a Journal Article 
520 3 |a 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. 
653 |a Urology 
653 |a Aldosterone 
653 |a Reagents 
653 |a Cytochrome 
653 |a Mutation 
653 |a Biosynthesis 
653 |a Therapeutic targets 
653 |a Life sciences 
653 |a Laparoscopy 
653 |a Amino acids 
653 |a Degradation 
653 |a Urological surgery 
653 |a Cell culture 
653 |a Destabilization 
653 |a Proteins 
653 |a Plasmids 
653 |a Tumor cells 
653 |a siRNA 
653 |a Ubiquitin-protein ligase 
653 |a Hospitals 
653 |a Phosphorylation 
653 |a Tumors 
653 |a Aldosterone synthase 
653 |a Pathogenesis 
653 |a Genetic screening 
653 |a Regulatory mechanisms (biology) 
653 |a Endoscopy 
653 |a Environmental 
773 0 |t Cellular and Molecular Life Sciences  |g vol. 82, no. 1 (Dec 2025), p. 27 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3149308699/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3149308699/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch