| Autophagy suppresses IL-1β signaling via the regulation of p62 stability. | |
| | |
MedLine Citation:
|
PMID: 22167182 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
ATG16L1 is an essential component of the autophagasome. The T300A allele of ATG16L1 is associated with the increased susceptibility to Crohns disease. In this study, we identified a novel function of ATG16L1, which suppresses signaling of the pro-inflammatory cytokine IL-1b. Deletion of ATG16L1 in mouse embryonic fibroblasts significantly amplifies IL-1b signal transduction cascades. This amplification is due to elevated p62 levels in ATG16L1-deficient cells. We found that ATG16L1 regulates p62 levels via both autolysosomal and proteasomal pathways. For proteasomal degradation, we found that Cullin-3 (Cul-3) is a E3 ubiquitin ligase of p62 and that ATG16L1 is essential for neddylation of Cul-3, a step required for Cul-3 activation. Taken together our data indicate that loss-of-function of ATG16L1 in fibroblasts results in a hyper-responsiveness to the IL-1b due to the increased p62 level. |
| | |
Authors:
|
Jongdae Lee; Hyeri Kim; Christine Quinley; Joanna Kim; Jose Gonzalez-Navajas; Ramnik Xavier; Eyal Raz |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-13 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of California, San Diego, United States; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A novel coenzyme B12-dependent interconversion of isovaleryl-CoA and pivalyl-CoA.
Next Document: Distinct roles of FANCO/RAD51C in DNA damage signaling and repair: implications for Fanconi anemia a...