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

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Title: AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arthritis synovial fibroblasts
Authors: Kato, Masaru Browse this author →KAKEN DB
Ospelt, Caroline Browse this author
Kolling, Christoph Browse this author
Shimizu, Tomohiro Browse this author
Kono, Michihito Browse this author
Yasuda, Shinsuke Browse this author →KAKEN DB
Michel, Beat A Browse this author
Gay, Renate E Browse this author
Gay, Steffen Browse this author
Klein, Kerstin Browse this author
Atsumi, Tatsuya Browse this author →KAKEN DB
Keywords: p97
histone deacetylase 6
cell death
Issue Date: 27-Sep-2016
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 7
Issue: 39
Start Page: 64221
End Page: 64232
Publisher DOI: 10.18632/oncotarget.11890
Abstract: 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.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 加藤 将

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