Role of cyclophilin B in activation of interferon regulatory factor-3 |
| |
Authors: | Obata Yoko Yamamoto Kazuo Miyazaki Masanobu Shimotohno Kunitada Kohno Shigeru Matsuyama Toshifumi |
| |
Affiliation: | Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Japan. |
| |
Abstract: | IRF-3 is a member of the interferon regulatory factors (IRFs) and plays a principal role in the induction of interferon-beta (IFN-beta) by virus infection. Virus infection results in the phosphorylation of IRF-3 by IkappaB kinase epsilon and TANK-binding kinase 1, leading to its dimerization and association with the coactivators CREB-binding protein/p300. The IRF-3 holocomplex translocates to the nucleus, where it induces IFN-beta. In the present study, we examined the molecular mechanism of IRF-3 activation. Using bacterial two-hybrid screening, we isolated molecules that interact with IRF-3. One of these was cyclophilin B, a member of the immunophilins with a cis-trans peptidyl-prolyl isomerase activity. A GST pull-down assay suggested that one of the autoinhibition domains of IRF-3 and the peptidyl-prolyl isomerase domain of cyclophilin B are required for the binding. A knockdown of cyclophilin B expression by RNA interference resulted in the suppression of virus-induced IRF-3 phosphorylation, leading to the inhibition of the subsequent dimerization, association with CREB-binding protein, binding to the target DNA element, and induction of IFN-beta. These findings indicate that cyclophilin B plays a critical role in IRF-3 activation. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|