화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.437, No.1, 179-184, 2013
IRF-1-binding site in the first intron mediates interferon-gamma-induced optineurin promoter activation
Optineurin is an adaptor protein involved in signal transduction, membrane vesicle trafficking and autophagy. Optineurin expression is induced by cytokines. Previously live have shown that tumor necrosis factor-alpha activates optineurin promoter through NF-kappa B-binding site in the core promoter. However, this promoter was not activated by interferon-gamma. Here, we report identification of a functional IRF-1-binding site in the first intron of human optineurin gene that mediates interferon-gamma-induced activation of the promoter. Optineurin promoter, containing the contiguous intronic sequences with IRF-1 responsive sites, is strongly activated by IRF-1. Mutational inactivation of IRF-1 site resulted in loss of activation of the promoter by interferon-gamma and also by IRF-1. We also show that IRF-1 cooperates with NF-kappa B to activate optineurin promoter. The synergistic effect of these two transcription factors (IRF-1 and NF-kappa B) may be involved in cooperative induction of optineurin promoter by interferon-gamma and tumor necrosis factor-alpha. (C) 2013 Elsevier Inc. All rights reserved.