| First Author | Yu C | Year | 2007 |
| Journal | Mol Cell | Volume | 25 |
| Issue | 5 | Pages | 765-78 |
| PubMed ID | 17349961 | Mgi Jnum | J:120086 |
| Mgi Id | MGI:3703842 | Doi | 10.1016/j.molcel.2007.01.025 |
| Citation | Yu C, et al. (2007) An essential function of the SRC-3 coactivator in suppression of cytokine mRNA translation and inflammatory response. Mol Cell 25(5):765-78 |
| abstractText | 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 LPS, SRC-3(-/-) macrophages produce significantly more proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1beta 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-1beta 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. |
