An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response
York, Brian（Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston）
Wang, Shu（Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston）
Feng, Qin（Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston）
Xu, Jianming（Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston）
O'Malley, Bert W.（Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston）
- 生命科学－已发表论文 
Steroid receptor coactivator-3 (SRC-3) is a transcriptional coactivator for nuclear receptors and other transcription factors. Although multiple physiological roles of SRC-3 have been revealed, its involvement in the inflammatory process remains unclear. Herein we show that SRC-3(-/-) mice are markedly hypersensitive to LPS-induced endotoxic shock. In response to LIPS, SRC-3(-/-) macrophages produce significantly more proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1 beta than wild-type controls, although they express similar amounts of cytokine mRNAs, suggesting that SRC-3 can exert effects at translational levels. Increased heavy polysome-associated TNF-alpha and IL-10 mRNAs in SRC-3(-/-) macrophages implicate SRC-3 as a translational repressor. SRC-3 may cooperate with other translational repressors such as TIA-1 and TIAR to regulate cytokine mRNA translation. Collectively, our studies reveal an essential function of SRC-3 as a coordinator of inflammatory mRNA translation and as a physiologic protective factor against the lethal endotoxic shock triggered by an acute inflammatory response.
CitationMOLECULAR CELL，Volume 25, Issue 5, 9 March 2007, Pages 765-778
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