AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts

Kato, Masaru; Ospelt, Caroline; Kolling, Christoph; Shimizu, Tomohiro; Kono, Michihito; Yasuda, Shinsuke; Michel, Beat A; Gay, Renate E; Gay, Steffen; Klein, Kerstin; Atsumi, Tatsuya

AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts

Kato, Masaru; Ospelt, Caroline; Kolling, Christoph et al.

Oncotarget, 2016, 7(39), 64221-64232

Permalink : https://hdl.handle.net/2115/64006

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アクセス権	open access
URI	https://hdl.handle.net/2115/64006
タイトル	AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts
著者	Kato, Masaru ; Ospelt, Caroline ; Kolling, Christoph ; Shimizu, Tomohiro ; Kono, Michihito ; Yasuda, Shinsuke ; Michel, Beat A ; Gay, Renate E ; Gay, Steffen ; Klein, Kerstin ; Atsumi, Tatsuya
e-Rad_Researcher 10755896 著者名 Kato, Masaru
著者名 Ospelt, Caroline
著者名 Kolling, Christoph
著者名 Shimizu, Tomohiro
著者名 Kono, Michihito
e-Rad_Researcher 00374231 著者名 Yasuda, Shinsuke
著者名 Michel, Beat A
著者名 Gay, Renate E
著者名 Gay, Steffen
著者名 Klein, Kerstin
e-Rad_Researcher 20301905 著者名 Atsumi, Tatsuya
言語	英語
キーワード	p97
	histone deacetylase 6
	polyubiquitin
	cell death
	autophagy
発行日	2016-09-27
出版者	Impact Journals
収録物名	Oncotarget
巻(号)	7(39)
ページ	64221-64232
抄録	Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction partner histone deacetylase 6 (HDAC6) had no effect. Furthermore, silencing of p97 in RASFs increased not only rates of apoptotic cell death induced by TRAIL but also induced an autophagy-associated cell death during ER stress that was accompanied by the formation of polyubiquitinated protein aggregates and large vacuoles. Finally, we demonstrated an anti-arthritic effect of siRNAs targeting p97 in collagen-induced arthritis in rats. Our data indicate that p97 may be a new potential target in the treatment of RA.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 3.0 Unported
PISSN	1949-2553
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.18632/oncotarget.11890