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Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons
| 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) |
| URI: | http://hdl.handle.net/2115/54867 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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