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RNF144A inhibits autophagy by targeting BECN1 for degradation during L. monocytogenes infection

Bo Yang1,2, Mengyang Shen1,2, Chen Lu1,2

  • 1Xinxiang Key Laboratory of Inflammation and Immunology, School of Medical Technology, Xinxiang Medical University, Xinxiang, Henan, China.

Autophagy
|November 28, 2024
PubMed

Insights

Ring finger protein 144A (RNF144A) promotes Listeria monocytogenes infection by degrading Beclin 1 (BECN1), a key autophagy regulator. RNF144A deficiency protects mice by inhibiting innate immune responses and enhancing autophagy.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Listeria monocytogenes (Lm) is a model pathogen for studying host defense against intracellular bacteria.
  • Autophagy is crucial for host defense, with BECN1 (beclin 1) being a key initiator protein.
  • Post-translational modifications of BECN1 regulate autophagy, impacting host-pathogen interactions.

Purpose of the Study:

  • To investigate the role of RNF144A (ring finger protein 144A) in Lm infection and autophagy.
  • To elucidate the mechanism by which RNF144A influences BECN1-mediated autophagy during Lm infection.

Main Methods:

  • Utilized RNF144A-induced Lm infection models in mice.
  • Investigated autophagy flux using inhibitors like bafilomycin A1 (Baf A1) and chloroquine (CQ).
  • Performed co-immunoprecipitation and ubiquitination assays to study RNF144A-BECN1 interactions and BECN1 ubiquitination.

Main Results:

  • RNF144A promotes Lm infection independently of STING1 but dependent on autophagy.
  • RNF144A deficiency in mice confers protection against Lm infection by inhibiting innate immunity.
  • RNF144A interacts with BECN1, promoting its K48-linked ubiquitination and proteasomal degradation, thereby reducing autophagosome accumulation.

Conclusions:

  • RNF144A acts as a novel regulator promoting intracellular bacterial infection by inhibiting BECN1-dependent autophagy.
  • RNF144A-mediated BECN1 degradation at specific sites (K117, K427) is critical for its function in autophagy and Lm infection.
  • Findings offer insights into host defense mechanisms against intracellular bacteria via autophagy regulation.
Keywords:
Autophagosome accumulationE3 ligaseautophagy-related genesintracellular bacterialpost-translational modificationring finger proteins

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