TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity

Kimura, Tomonori, Jain, Ashish, Choi, Seong Won, Mandell, Michael A., Schroder, Kate, Johansen, Terje and Deretic, Vojo (2015) TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity. Journal of Cell Biology, 210 6: 973-989. doi:10.1083/jcb.201503023


Author Kimura, Tomonori
Jain, Ashish
Choi, Seong Won
Mandell, Michael A.
Schroder, Kate
Johansen, Terje
Deretic, Vojo
Title TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity
Journal name Journal of Cell Biology   Check publisher's open access policy
ISSN 0021-9525
1540-8140
Publication date 2015-09
Sub-type Article (original research)
DOI 10.1083/jcb.201503023
Open Access Status DOI
Volume 210
Issue 6
Start page 973
End page 989
Total pages 17
Place of publication New York, NY, United States
Publisher Rockefeller University Press
Collection year 2016
Language eng
Abstract The present paradigms of selective autophagy in mammalian cells cannot fully explain the specificity and selectivity of autophagic degradation. In this paper, we report that a subset of tripartite motif (TRIM) proteins act as specialized receptors for highly specific autophagy (precision autophagy) of key components of the inflammasome and type I interferon response systems. TRIM20 targets the inflammasome components, including NLRP3, NLRP1, and pro–caspase 1, for autophagic degradation, whereas TRIM21 targets IRF3. TRIM20 and TRIM21 directly bind their respective cargo and recruit autophagic machinery to execute degradation. The autophagic function of TRIM20 is affected by mutations associated with familial Mediterranean fever. These findings broaden the concept of TRIMs acting as autophagic receptor regulators executing precision autophagy of specific cytoplasmic targets. In the case of TRIM20 and TRIM21, precision autophagy controls the hub signaling machineries and key factors, inflammasome and type I interferon, directing cardinal innate immunity response systems in humans.
Keyword Familial mediterranean fever
Selective autophagy
Il-1-beta production
Isolation membrane
Interferon-gamma
Epithelial-cells
Dap-kinase
Protein
Ulk1
Phosphorylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
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