[PDF][PDF] Formation of an IKKα-dependent transcription complex is required for estrogen receptor-mediated gene activation
KJ Park, V Krishnan, BW O'Malley, Y Yamamoto… - Molecular cell, 2005 - cell.com
KJ Park, V Krishnan, BW O'Malley, Y Yamamoto, RB Gaynor
Molecular cell, 2005•cell.comThe IκB kinases IKKα and IKKβ regulate distinct cytoplasmic and nuclear events that are
critical for cytokine-mediated activation of the NF-κB pathway. Because the IKKs have
previously been demonstrated to associate with the nuclear hormone receptor coactivator
AIB1/SRC-3, the question of whether either IKKα or IKKβ may be involved in increasing the
expression of hormone-responsive genes was addressed. We demonstrated that IKKα, in
conjunction with ERα and AIB1/SRC-3, is important in activating the transcription of estrogen …
critical for cytokine-mediated activation of the NF-κB pathway. Because the IKKs have
previously been demonstrated to associate with the nuclear hormone receptor coactivator
AIB1/SRC-3, the question of whether either IKKα or IKKβ may be involved in increasing the
expression of hormone-responsive genes was addressed. We demonstrated that IKKα, in
conjunction with ERα and AIB1/SRC-3, is important in activating the transcription of estrogen …
Summary
The IκB kinases IKKα and IKKβ regulate distinct cytoplasmic and nuclear events that are critical for cytokine-mediated activation of the NF-κB pathway. Because the IKKs have previously been demonstrated to associate with the nuclear hormone receptor coactivator AIB1/SRC-3, the question of whether either IKKα or IKKβ may be involved in increasing the expression of hormone-responsive genes was addressed. We demonstrated that IKKα, in conjunction with ERα 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 IKKα, ERα, and AIB1/SRC-3 to estrogen-responsive promoters and increased IKKα phosphorylation of ERα, AIB1/SRC-3, and histone H3. These results suggest that IKKα plays a major role in regulating the biological effects of estrogen via its promoter association and modification of components of the transcription complex.
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