Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation.
The IkappaB kinases IKKalpha and IKKbeta regulate distinct cytoplasmic and nuclear events that are critical for cytokine-mediated activation of the NF-kappaB pathway. Because the IKKs have previously been demonstrated to associate with the nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either IKKalpha or IKKbeta may be involved in increasing the expression of hormone-responsive genes was addressed. We demonstrated that IKKalpha, in conjunction with ERalpha and AIB1/SRC-3, is important in activating the transcription of estrogen-responsive genes, including cyclin D1 and c-myc, to result in the enhanced proliferation of breast cancer cells. Estrogen treatment facilitated the association of IKKalpha, ERalpha, and AIB1/SRC-3 to estrogen-responsive promoters and increased IKKalpha phosphorylation of ERalpha, AIB1/SRC-3, and histone H3. These results suggest that IKKalpha plays a major role in regulating the biological effects of estrogen via its promoter association and modification of components of the transcription complex.[1]References
- Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Park, K.J., Krishnan, V., O'Malley, B.W., Yamamoto, Y., Gaynor, R.B. Mol. Cell (2005) [Pubmed]
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