272 : The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone Hsp90

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

doi:10.1016/j.cyto.2013.06.275

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272 : The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone Hsp90

Abstract

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272 : The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone Hsp90

Chenhui Wang, Ling Wu, Katarzyna Bulek, Bradley N Martin, Jarod A Zepp, Zizhen Kang, Caini Liu, Tomasz Herjan, Saurav Misra, Julie A Carman, …

Cytokine (Philadelphia, Pa.), Vol.63(3), pp.307-307

09/2013

DOI: 10.1016/j.cyto.2013.06.275

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Abstract

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 TH17 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.

Details

Title: Subtitle: 272 : The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone Hsp90
Creators: Chenhui Wang - Cleveland Clinic
Ling Wu - Case Western Reserve University
Katarzyna Bulek - Cleveland Clinic
Bradley N Martin - Case Western Reserve University
Jarod A Zepp - Cleveland Clinic
Zizhen Kang - Cleveland Clinic
Caini Liu - Cleveland Clinic
Tomasz Herjan - Cleveland Clinic
Saurav Misra - Cleveland Clinic
Julie A Carman - Bristol-Myers Squibb
Ji Gao - Bristol-Myers Squibb
Ashok Dongre - Bristol-Myers Squibb
Shujie Han - Emory University
Kevin D Bunting - Emory University
Jennifer S Ko - Cleveland Clinic
Hui Xiao - Chinese Academy of Sciences
Vijay K Kuchroo - Brigham and Women's Hospital
Wenjun Ouyang - Genentech
Xiaoxia Li - Cleveland Clinic
Resource Type: Abstract
Publication Details: Cytokine (Philadelphia, Pa.), Vol.63(3), pp.307-307
DOI: 10.1016/j.cyto.2013.06.275
ISSN: 1043-4666
eISSN: 1096-0023
Publisher: Elsevier Ltd
Language: English
Date published: 09/2013
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984201118602771

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