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The E3 Ubiquitin Ligase RNF123 Mediates Pathological Cardiac Hypertrophy by Ubiquitinating PRDX1 and Upregulating

Qinyan Wang1,2, Xiaochen Guo2, Jiachen Xu1

  • 1Department of Cardiology and Medical Research Center, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Acta Physiologica (Oxford, England)
|May 10, 2026
PubMed

Insights

RNF123 E3 ligase targets PRDX1 for degradation, promoting cardiac hypertrophy. Inhibiting RNF123 may offer a new treatment for heart failure (HF) by reducing pathological cardiac remodeling.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Ubiquitin Biology

Background:

  • Pathological cardiac hypertrophy is a major risk factor for heart failure (HF).
  • Protein ubiquitination plays a critical role in the pathogenesis of HF.
  • The E3 ubiquitin ligase RNF123's role in HF is investigated.

Purpose of the Study:

  • To investigate the role of RNF123 in cardiac hypertrophy and heart failure.
  • To elucidate the molecular mechanism by which RNF123 contributes to cardiac pathogenesis.

Main Methods:

  • Induction of heart failure in mice using angiotensin II (Ang II) infusion and transverse aortic constriction (TAC).
  • Utilized liquid chromatography-tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP) to identify RNF123 interacting proteins.
  • Performed in vitro studies using neonatal rat ventricular myocytes (NRVMs) with RNF123 knockdown or overexpression.

Main Results:

  • RNF123 expression was upregulated in cardiomyocytes during induced cardiac hypertrophy.
  • RNF123 deficiency attenuated cardiac hypertrophy and dysfunction in vivo and in vitro.
  • RNF123 directly ubiquitinates PRDX1, leading to its proteasomal degradation and increased ROS levels, driving hypertrophy.

Conclusions:

  • Cardiomyocyte RNF123 mediates pathological cardiac hypertrophy by ubiquitinating PRDX1.
  • Targeting RNF123 presents a potential therapeutic strategy for treating heart failure.
Abstract

Keywords:
PRDX1RNF123angiotensin IIcardiac hypertrophyheart failuretransverse aortic constriction

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