Histone H3 phosphorylation by ikk-α is critical for cytokine-induced gene expression

Yamamoto Yumi, Udit N. Verma, Shashi Prajapati, Kwak Youn-Tae, Richard B. Gaynor

Research output: Contribution to journalArticlepeer-review

510 Scopus citations


Cytokine-induced activation of the IκB kinases (IKK) IKK-α and IKK-β is a key step involved in the activation of the NF-κB pathway. Gene-disruption studies of the murine IKK genes have shown that IKK-β, but not IKK-α, is critical for cytokine-induced IκB degradation. Nevertheless, mouse embryo fibroblasts deficient in IKK-α are defective in the induction of NF-κB-dependent transcription. These observations raised the question of whether IKK-α might regulate a previously undescribed step to activate the NF-κB pathway that is independent of its previously described cytoplasmic role in the phosphorylation of IκBα. Here we show that IKK-α functions in the nucleus to activate the expression of NF-κB-responsive genes after stimulation with cytokines. IKK-α interacts with CREB-binding protein and in conjunction with Rel A is recruited to NF-κB-responsive promoters and mediates the cytokine-induced phosphorylation and subsequent acetylation of specific residues in histone H3. These results define a new nuclear role of IKK-α in modifying histone function that is critical for the activation of NF-κB-directed gene expression.

Original languageEnglish (US)
Pages (from-to)655-659
Number of pages5
Issue number6940
StatePublished - Jun 5 2003

ASJC Scopus subject areas

  • General


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