Related Experiment Video

Updated: Jan 12, 2026

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination
08:13

In-vitro Reconstitution of Bacterial Ubiquitination and VCP/p97-mediated Elimination

Published on: January 2, 2026

91

ENKD1 attenuates antibacterial immunity by facilitating TRIM21-mediated RUBCN degradation to suppress LC3-associated

Caimeng Song1, Lulu Sun1, Jie Wang1

  • 1Center for Cell Structure and Function, College of Life Sciences, Shandong Normal University, Jinan 250358, China.

Proceedings of the National Academy of Sciences of the United States of America
|November 4, 2025
PubMed

Insights

Enkurin domain-containing protein 1 (ENKD1) suppresses Microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP). ENKD1 deficiency enhances antibacterial immunity against pathogens like Listeria, Salmonella, and Francisella.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP) is crucial for host defense against intracellular pathogens.
  • The regulatory mechanisms governing LAP are not fully understood.

Purpose of the Study:

  • To identify novel regulators of LAP.
  • To elucidate the role of enkurin domain-containing protein 1 (ENKD1) in LAP and host defense.

Main Methods:

  • Macrophage infection models with Listeria monocytogenes, Salmonella typhimurium, and Francisella novicida.
  • Analysis of ENKD1 expression, LAP activity, reactive oxygen species production, and phagosome-lysosome fusion.
  • In vivo studies using ENKD1-deficient mice.
  • Co-immunoprecipitation and ubiquitination assays to identify protein interactions.

Main Results:

  • ENKD1 expression is downregulated during infection with L. monocytogenes, S. typhimurium, and F. novicida.
  • ENKD1-deficient macrophages exhibit enhanced LAP, increased reactive oxygen species, and improved phagosome-lysosome fusion, leading to better bacterial clearance.
  • ENKD1-deficient mice show improved bacterial clearance and survival.
  • ENKD1 interacts with TRIM21 to promote RUBCN degradation via K48-linked polyubiquitination, suppressing LAP.

Conclusions:

  • ENKD1 acts as a negative regulator of LAP.
  • The ENKD1-TRIM21-RUBCN axis suppresses antibacterial immunity.
  • Targeting this axis may offer therapeutic strategies to enhance host defense against intracellular pathogens.
Keywords:
ENKD1LC3-associated phagocytosisRUBCNTRIM21antibacterial immunity

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