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Updated: Sep 19, 2025

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

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E3 ubiquitin ligase Listerin regulates macrophage cholesterol efflux and atherosclerosis by targeting ABCA1

Lei Cao1, Jie Zhang1, Liwen Yu1

  • 1State Key Laboratory for Innovation and Transformation of Luobing Theory; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Department of Cardiology and.

The Journal of Clinical Investigation
|June 17, 2025
PubMed

Insights

Listerin E3 ubiquitin protein ligase 1 (Listerin) protects against atherosclerosis by stabilizing ABCA1, a key protein for cholesterol removal. This mechanism enhances macrophage cholesterol efflux and reduces plaque development, offering a new therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Metabolism

Background:

  • Atherosclerosis involves disrupted cholesterol metabolism and macrophage foam cell formation.
  • Impaired cholesterol efflux from macrophages is a critical step in atherosclerosis progression.

Purpose of the Study:

  • To identify novel regulators of macrophage cholesterol metabolism in atherosclerosis.
  • To elucidate the role of Listerin E3 ubiquitin protein ligase 1 (Listerin) in atherosclerosis pathogenesis.

Main Methods:

  • Single-cell and bulk RNA sequencing.
  • Macrophage-specific knockout (KO) and overexpression mouse models.
  • Analysis of ABCA1 ubiquitination and degradation pathways.
  • In vitro studies using THP-1 cells.

Main Results:

  • Listerin expression is upregulated during atherosclerosis progression.
  • Listerin deficiency impairs cholesterol efflux, promotes foam cell formation, and exacerbates atherosclerotic plaque features.
  • Listerin stabilizes ABCA1 through K63-linked polyubiquitination, preventing its lysosomal degradation.
  • ABCA1 agonist treatment rescues cholesterol efflux in Listerin-deficient macrophages.

Conclusions:

  • Listerin acts as a protective factor in atherosclerosis by stabilizing ABCA1.
  • Targeting Listerin-mediated ABCA1 ubiquitination represents a potential therapeutic strategy for enhancing cholesterol efflux and treating atherosclerosis.

Keywords:
AtherosclerosisCardiologyMetabolismUbiquitin-proteosome system

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