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Publication : IRGM governs the core autophagy machinery to conduct antimicrobial defense.

First Author  Chauhan S Year  2015
Journal  Mol Cell Volume  58
Issue  3 Pages  507-21
PubMed ID  25891078 Mgi Jnum  J:347306
Mgi Id  MGI:7622110 Doi  10.1016/j.molcel.2015.03.020
Citation  Chauhan S, et al. (2015) IRGM governs the core autophagy machinery to conduct antimicrobial defense. Mol Cell 58(3):507-21
abstractText  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.
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