| The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90. | |
| | |
MedLine Citation:
|
PMID: 23202271 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Act1 is an essential adaptor in interleukin 17 (IL-17)-mediated signaling and is recruited to the receptor for IL-17 after stimulation with IL-17. Here we found that Act1 was a 'client' protein of the molecular chaperone hsp90. The D10N variant of Act1 (Act1(D10N)) that is linked to susceptibility to psoriasis was defective in its interaction with hsp90, which resulted in a global loss of Act1 function. Act1-deficient mice modeled the mechanistic link between loss of Act1 function and susceptibility to psoriasis. Although Act1 was necessary for IL-17-mediated inflammation, Act1-deficient mice had a hyperactive response of the T(H)17 subset of helper T cells and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17 signaling, IL-22 was the main contributor to skin inflammation, which provides a molecular mechanism for the association of Act1(D10N) with psoriasis susceptibility. |
| | |
Authors:
|
Chenhui Wang; Ling Wu; Katarzyna Bulek; Bradley N Martin; Jarod A Zepp; Zizhen Kang; Caini Liu; Tomasz Herjan; Saurav Misra; Julie A Carman; Ji Gao; Ashok Dongre; Shujie Han; Kevin D Bunting; Jennifer S Ko; Hui Xiao; Vijay K Kuchroo; Wenjun Ouyang; Xiaoxia Li |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-12-02 |
Journal Detail:
|
Title: Nature immunology Volume: 14 ISSN: 1529-2916 ISO Abbreviation: Nat. Immunol. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2012-12-14 Completed Date: 2013-03-01 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 100941354 Medline TA: Nat Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 72-81 Citation Subset: IM |
Affiliation:
|
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Line Connexin 43 / genetics, immunology, metabolism* Disease Models, Animal Genetic Predisposition to Disease HSP90 Heat-Shock Proteins / metabolism* Humans Interleukin-17 / metabolism Mice Mice, Knockout Molecular Chaperones / genetics, metabolism* Mutation / genetics Peptide Fragments / genetics, immunology, metabolism* Polymorphism, Genetic Protein Binding / genetics, immunology Psoriasis / genetics, immunology* Signal Transduction Th17 Cells / immunology* |
| Grant Support | |
ID/Acronym/Agency:
|
1P01 HL103453/HL/NHLBI NIH HHS; 1R01NS071996/NS/NINDS NIH HHS; P01 HL103453/HL/NHLBI NIH HHS; R01 GM080271/GM/NIGMS NIH HHS; R01 NS071996/NS/NINDS NIH HHS; T32 AI89474-1/AI/NIAID NIH HHS; T32 GM007250/GM/NIGMS NIH HHS; UL1 TR000439/TR/NCATS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/ACT1 protein; 0/Connexin 43; 0/HSP90 Heat-Shock Proteins; 0/Interleukin-17; 0/Molecular Chaperones; 0/Peptide Fragments |
| Comments/Corrections | |
Comment In:
|
Nat Immunol. 2013 Jan;14(1):16-7
[PMID:
23238753
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells.
Next Document: Conformational states of the kinase Lck regulate clustering in early T cell signaling.