Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90

Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 variant (D10N) linked to psoriasis susceptibility is defective in its interaction...

Full description

Bibliographic Details
Main Authors:	Wang, Chenhui, Wu, Ling, Bulek, Katarzyna, Martin, Bradley N., Zepp, Jarod A., Kang, Zizhen, Liu, Caini, Herjan, Tomasz, Misra, Saurav, Carman, Julie A., Gao, Ji, Dongre, Ashok, Han, Shujie, Bunting, Kevin D., Ko, Jennifer S., Xiao, Hui, Kuchroo, Vijay K., Ouyang, Wenjun, Li, Xiaoxia
Format:	Online
Language:	English
Published:	2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522792/

id	pubmed-3522792
recordtype	oai_dc
spelling	pubmed-35227922013-07-01 Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90 Wang, Chenhui Wu, Ling Bulek, Katarzyna Martin, Bradley N. Zepp, Jarod A. Kang, Zizhen Liu, Caini Herjan, Tomasz Misra, Saurav Carman, Julie A. Gao, Ji Dongre, Ashok Han, Shujie Bunting, Kevin D. Ko, Jennifer S. Xiao, Hui Kuchroo, Vijay K. Ouyang, Wenjun Li, Xiaoxia Article Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 variant (D10N) linked to psoriasis susceptibility is defective in its interaction with Hsp90, resulting in a global loss of Act1 function. Act1-/- mice modeled the mechanistic link between Act1 loss of function and psoriasis susceptibility. Although Act1 is necessary for IL-17-mediated inflammation, Act1-/- mice exhibited a hyper TH17 response and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17-signaling, IL-22 is the main contributor to skin inflammation, providing a molecular mechanism for the association of Act1 (D10N) with psoriasis susceptibility. 2012-12-02 2013-01 /pmc/articles/PMC3522792/ /pubmed/23202271 http://dx.doi.org/10.1038/ni.2479 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Chenhui Wu, Ling Bulek, Katarzyna Martin, Bradley N. Zepp, Jarod A. Kang, Zizhen Liu, Caini Herjan, Tomasz Misra, Saurav Carman, Julie A. Gao, Ji Dongre, Ashok Han, Shujie Bunting, Kevin D. Ko, Jennifer S. Xiao, Hui Kuchroo, Vijay K. Ouyang, Wenjun Li, Xiaoxia
spellingShingle	Wang, Chenhui Wu, Ling Bulek, Katarzyna Martin, Bradley N. Zepp, Jarod A. Kang, Zizhen Liu, Caini Herjan, Tomasz Misra, Saurav Carman, Julie A. Gao, Ji Dongre, Ashok Han, Shujie Bunting, Kevin D. Ko, Jennifer S. Xiao, Hui Kuchroo, Vijay K. Ouyang, Wenjun Li, Xiaoxia Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
author_facet	Wang, Chenhui Wu, Ling Bulek, Katarzyna Martin, Bradley N. Zepp, Jarod A. Kang, Zizhen Liu, Caini Herjan, Tomasz Misra, Saurav Carman, Julie A. Gao, Ji Dongre, Ashok Han, Shujie Bunting, Kevin D. Ko, Jennifer S. Xiao, Hui Kuchroo, Vijay K. Ouyang, Wenjun Li, Xiaoxia
author_sort	Wang, Chenhui
title	Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
title_short	Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
title_full	Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
title_fullStr	Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
title_full_unstemmed	Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90
title_sort	psoriasis-associated variant act1 d10n with impaired regulation by hsp90
description	Act1 is an essential adaptor molecule in IL-17-mediated signaling and is recruited to the IL-17 receptor upon IL-17 stimulation. Here, we report that Act1 is a client protein of the molecular chaperone, Hsp90. The Act1 variant (D10N) linked to psoriasis susceptibility is defective in its interaction with Hsp90, resulting in a global loss of Act1 function. Act1-/- mice modeled the mechanistic link between Act1 loss of function and psoriasis susceptibility. Although Act1 is necessary for IL-17-mediated inflammation, Act1-/- mice exhibited a hyper TH17 response and developed spontaneous IL-22-dependent skin inflammation. In the absence of IL-17-signaling, IL-22 is the main contributor to skin inflammation, providing a molecular mechanism for the association of Act1 (D10N) with psoriasis susceptibility.
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522792/
_version_	1611940625151688704

Psoriasis-associated variant Act1 D10N with impaired regulation by Hsp90

Similar Items