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Sci. STKE, 14 May 2002
Vol. 2002, Issue 132, p. tw173
[DOI: 10.1126/stke.2002.132.tw173]

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TRANSCRIPTION IKK Links the Steroid Receptor Coactivator to Immune Responses

Steroid receptor coactivators (SRCs) were originally identified by their ability to interact and activate ligand-activated nuclear receptors. Wu et al. report that the components of the inhibitor of {kappa}B kinase (IKK) complex, which is responsible for the activation of NF-{kappa}B (a transcription factor that regulates genes involved in immune and survival responses), can be isolated in a complex with SRC-3. Cotransfection of a reporter gene containing an NF-{kappa}B-responsive promoter with SCR-3 and either IKKα or IKKβ stimulated gene expression more than did cotransfection of any of these three proteins alone. In these transfected cells, natural activator of the NF-{kappa}B pathway, tumor necrosis factor α (TNF-α), further increased reporter gene expression. Synergism between SRC-3 and IKK required the catalytic activity of IKK and IKKα and IKKβ phosphorylated SRC-3 in vitro. Phosphorylation of SRC-3 was stimulated by TNF-α, as was the nuclear localization of SRC-3 in response to TNF-α. Overexpression of SRC-3 stimulated the expression of caspase 4 and caspase 5, and immune responses in SRC-3 null mice were compromised with a decrease in the expression of a known NF-{kappa}B target gene, further supporting a link between NF-{kappa}B and SRC-3. These results suggest that SRCs are not limited to be coactivators for only the ligand-activated family of nuclear receptors but are also regulators of NF-{kappa}B-mediated gene expression involved inflammatory response.

R.-C. Wu, J. Qin, Y. Hashimoto, J. Wong, J. Xu, S. Y. Tsai, M.-J. Tsai, B. W. O'Malley, Regulation of SCR-3 (pCIP/ACTR/AIB-1/Rac-3/TRAM-1) coactivator activity by I{kappa}B kinase. Mol. Cell. Biol. 22, 3549-3561 (2002). [Abstract] [Full Text]

Citation: IKK Links the Steroid Receptor Coactivator to Immune Responses. Sci. STKE 2002, tw173 (2002).


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