ISG15 modification of filamin B negatively regulates the type I interferon-induced JNK signalling pathway
- Authors
- Jeon, Young Joo; Choi, Joon Seok; Lee, Jung Yun; Yu, Kyung Ryun; Kim, Sangman Michael; Ka, Seung Hyeun; Oh, Kyu Hee; Kim, Keun Il; Zhang, Dong-Er; Bang, Ok Sun; Chung, Chin Ha
- Issue Date
- Apr-2009
- Publisher
- WILEY
- Keywords
- apoptosis; filamin B scaffold; ISG15; JNK signalling pathway; type I interferon
- Citation
- EMBO REPORTS, v.10, no.4, pp 374 - 380
- Pages
- 7
- Journal Title
- EMBO REPORTS
- Volume
- 10
- Number
- 4
- Start Page
- 374
- End Page
- 380
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13790
- DOI
- 10.1038/embor.2009.23
- ISSN
- 1469-221X
1469-3178
- Abstract
- Interferon (IFN)-induced signalling pathways have essential functions in innate immune responses. In response to type I IFNs, filamin B tethers RAC1 and a Jun N-terminal kinase (JNK)-specific mitogen-activated protein kinase ( MAPK) module-MEKK1, MKK4 and JNK-and thereby promotes the activation of JNK and JNK-mediated apoptosis. Here, we show that type I IFNs induce the conjugation of filamin B by interferon-stimulated gene 15 (ISG15). ISGylation of filamin B led to the release of RAC1, MEKK1 and MKK4 from the scaffold protein and thus to the prevention of sequential activation of the JNK cascade. By contrast, blockade of filamin B ISGylation by substitution of Lys 2467 with arginine or by knockdown of ubiquitin-activating enzyme E1-like (UBEL1) prevented the release of the signalling molecules from filamin B, resulting in persistent promotion of JNK activation and JNK-mediated apoptosis. These results indicate that filamin B ISGylation acts as a negative feedback regulatory gate for the desensitization of type I IFN-induced JNK signalling.
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