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Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons

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Title: Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons
Authors: Muromoto, Ryuta Browse this author →KAKEN DB
Nakajima, Maiko Browse this author
Hirashima, Koki Browse this author
Hirao, Toru Browse this author
Kon, Shigeyuki Browse this author
Shimoda, Kazuya Browse this author →KAKEN DB
Oritani, Kenji Browse this author →KAKEN DB
Matsuda, Tadashi Browse this author →KAKEN DB
Issue Date: 25-Oct-2013
Publisher: Amer soc biochemistry molecular biology inc
Journal Title: Journal of biological chemistry
Volume: 288
Issue: 43
Start Page: 30969
End Page: 30979
Publisher DOI: 10.1074/jbc.M113.485847
PMID: 24043623
Abstract: Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK family kinase, has been reported to bind to and stabilize IFNR, indicating that TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1 resulted in suppression of IFN-induced phosphorylation of STAT proteins and their transcriptional activation. Importantly, JAB1 knockdown induced the activation of SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the enhancement of covalent modification of CUL1 with the ubiquitin-like protein NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8 knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme inhibitor resulted in increased IFNR protein concomitantly with a reduction of NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment enhanced the susceptibility to IFN-alpha in HeLa cells. These data suggest that the NEDD8 modification pathway is involved in the proteolysis of IFNR and that JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway.
Rights: This research was originally published in the Journal of biological chemistry. Muromoto R, et al. Jun activation domain-binding protein 1 (JAB1) is required for the optimal response to interferons. The Journal of biological chemistry. 2013; 288(43):30969-79. ©2013 the American Society for Biochemistry and Molecular Biology.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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