IRGM governs the core autophagy machinery to conduct antimicrobial defense.

IRGM, encoded by a uniquely human gene conferring risk for inflammatory diseases, affects autophagy through an unknown mechanism. Here, we show how IRGM controls autophagy. IRGM interacts with ULK1 and Beclin 1 and promotes their co-assembly thus governing the formation of autophagy initiation complexes. We further show that IRGM interacts ...
with pattern recognition receptors including NOD2. IRGM, NOD2, and ATG16L1, all of which are Crohn's disease risk factors, form a molecular complex to modulate autophagic responses to microbial products. NOD2 enhances K63-linked polyubiquitination of IRGM, which is required for interactions of IRGM with the core autophagy factors and for microbial clearance. Thus, IRGM plays a direct role in organizing the core autophagy machinery to endow it with antimicrobial and anti-inflammatory functions.
Mesh Terms:
Anti-Infective Agents, Apoptosis Regulatory Proteins, Autophagy, Blotting, Western, Carrier Proteins, Cell Line, Tumor, Crohn Disease, GTP-Binding Proteins, Gene Expression, HCT116 Cells, HEK293 Cells, HT29 Cells, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Microscopy, Confocal, Nod2 Signaling Adaptor Protein, Protein Binding, Protein-Serine-Threonine Kinases, RNA Interference, Receptors, Pattern Recognition, Reverse Transcriptase Polymerase Chain Reaction, U937 Cells, Ubiquitination
Mol. Cell
Date: May. 07, 2015
Download Curated Data For This Publication
191818
Switch View:
  • Interactions 18