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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL
| Title: | NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL |
| Authors: | Miyazaki, Masaya Browse this author | | Nishihara, Hiroshi Browse this author →KAKEN DB | | Hasegawa, Hideki Browse this author | | Tashiro, Masato Browse this author | | Wang, Lei Browse this author | | Kimura, Taichi Browse this author →KAKEN DB | | Tanino, Mishie Browse this author →KAKEN DB | | Tsuda, Masumi Browse this author →KAKEN DB | | Tanaka, Shinya Browse this author →KAKEN DB |
| Keywords: | NS1 | | CrkL | | CrkII | | NS1-BP | | Cell proliferation | | ERK |
| Issue Date: | 29-Nov-2013 |
| Publisher: | Academic press inc elsevier science |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 441 |
| Issue: | 4 |
| Start Page: | 953 |
| End Page: | 957 |
| Publisher DOI: | 10.1016/j.bbrc.2013.11.011 |
| PMID: | 24220336 |
| Abstract: | The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERR and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated. (C) 2013 Elsevier Inc. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/54561 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 西原 広史
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