Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis View Full Text


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Article Info

DATE

2022-06-14

AUTHORS

Apeksha Bharatgiri Goswami, Dimitrije Karadarević, Natalia Castaño-Rodríguez

ABSTRACT

The human immunity-related GTPase M (IRGM) is a GTP-binding protein that regulates selective autophagy including xenophagy and mitophagy. IRGM impacts autophagy by (1) affecting mitochondrial fusion and fission, (2) promoting the co-assembly of ULK1 and Beclin 1, (3) enhancing Beclin 1 interacting partners (AMBRA1, ATG14L1, and UVRAG), (4) interacting with other key proteins (ATG16L1, p62, NOD2, cGAS, TLR3, and RIG-I), and (5) regulating lysosomal biogenesis. IRGM also negatively regulates NLRP3 inflammasome formation and therefore, maturation of the important pro-inflammatory cytokine IL-1β, impacting inflammation and pyroptosis. Ultimately, this affords protection against chronic inflammatory diseases. Importantly, ten IRGM polymorphisms (rs4859843, rs4859846, rs4958842, rs4958847, rs1000113, rs10051924, rs10065172, rs11747270, rs13361189, and rs72553867) have been associated with human inflammatory disorders including cancer, which suggests that these genetic variants are functionally relevant to the autophagic and inflammatory responses. The current review contextualizes IRGM, its modulation of autophagy, and inflammation, and emphasizes the role of IRGM as a cross point of immunity and tumorigenesis. More... »

PAGES

785-795

References to SciGraph publications

  • 2014-03-05. Association between genetic variants in the IRGM gene and tuberculosis in a Korean population in INFECTION
  • 2020-08-03. Mammalian Atg8 proteins and the autophagy factor IRGM control mTOR and TFEB at a regulatory node critical for responses to pathogens in NATURE CELL BIOLOGY
  • 1999-12. Induction of autophagy and inhibition of tumorigenesis by beclin 1 in NATURE
  • 2005-10-31. The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the cell autonomous resistance mechanism in the human lineage in GENOME BIOLOGY
  • 2014-01-28. Mycobacterium leprae Upregulates IRGM Expression in Monocytes and Monocyte-Derived Macrophages in INFLAMMATION
  • 2013-11-22. Autophagy Gene Polymorphism is Associated with Susceptibility to Leprosy by Affecting Inflammatory Cytokines in INFLAMMATION
  • 2015-02-24. Elevated expression of immunity-related GTPase family M in gastric cancer in TUMOR BIOLOGY
  • 2009-06-03. Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach in GENES & IMMUNITY
  • 2015-01-26. IFNg-induced Irgm1 promotes tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy in ONCOGENE
  • 2016-12-29. Autophagy-related IRGM genes confer susceptibility to ankylosing spondylitis in a Chinese female population: a case–control study in GENES & IMMUNITY
  • 2014-05-24. Functional IRGM polymorphism is associated with language impairment in glioma and upregulates cytokine expressions in TUMOR BIOLOGY
  • 2008-08-24. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease in NATURE GENETICS
  • 2016-04-20. Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection in BMC BIOLOGY
  • 2021-01-28. IRGM1 links mitochondrial quality control to autoimmunity in NATURE IMMUNOLOGY
  • 2011-01-30. A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease in NATURE GENETICS
  • 2008-12-18. Polymorphism of the IRGM Gene Might Predispose to Fistulizing Behavior in Crohn's Disease in THE AMERICAN JOURNAL OF GASTROENTEROLOGY
  • 2017-10-05. A haplotypic variant at the IRGM locus and rs11747270 are related to the susceptibility for chronic periodontitis in INFLAMMATION RESEARCH
  • 2010-11-21. Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria in NATURE CELL BIOLOGY
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    http://scigraph.springernature.com/pub.10.1007/s00011-022-01595-x

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