期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 89-90, 期 1-5, 页码 131-137出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2004.03.092
关键词
C/EBP beta; gamma-interferon; 1 alpha-hydroxylase; transcriptional control
资金
- NIAMS NIH HHS [AR45283] Funding Source: Medline
gamma-Interferon [gamma-IFN] induction of macrophage 1alpha-hydroxylase mRNA and activity causes severe hypercalcemia in granulomatous disorders. These studies demonstrate transcriptional regulation. gamma-IFN induces the activity of the murine 1alpha-hydroxylase [-1651; +22] promoter in the murine macrophage cell line Raw 264.7 only after a 24 h exposure. This slow kinetics is incompatible with classical gamma-IFN-mediated trans activation. In fact, y-IFN response mapped to the minimal [-85; +11] promoter, which lacks GAS or ISRE sites but contains a putative C/EBPbeta site. C/EBPbeta is a gamma-IFN inducible gene and a novel mediator of gamma-IFN-regulated transcription. As expected for a C/EBPbeta-driven transcription, ectopic C/EBPbeta expression was sufficient to increase 1alpha-hydroxylase activity, enhance minimal promoter activity and potentiate the induction of this promoter by gamma-IFN. Importantly, the dominant negative C/EBPbeta isoform antagonized C/EBPbeta-transcriptional activity. gamma-IFN induction of C/EBPbeta expression is not sufficient for gamma-IFN induction of minimal promoter activity. There is also a cell-specific induction of C/EBPbeta-transcriptional activity by gamma-IFN. In Raw cells, specific inhibition of gamma-IFN induction of endogenous-C/EBPbeta phosphorylation by MEKK I markedly reduced basal promoter activity and the response to gamma-IFN. We conclude that gamma-IFN-induction of C/EBPbeta expression and activation by phosphorylation contributes to gamma-IFN-transcriptional control of 1alpha-hydroxylase expression in murine macrophages. (C) 2004 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据