IKK-i/IKKε controls constitutive, cancer cell-associated NF-κB activity via regulation of Ser-536 p65/RelA phosphorylation

Mazhar Adli, Albert S. Baldwin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Nuclear factor κB (NF-κB) has been studied extensively as an inducible transcriptional regulator of the immune and inflammatory response. NF-κB activation downstream of lipopolysaccharide or cytokine stimulation is controlled by the IκB kinase complex, which contains IKKα and IKKβ. Significantly, the constitutive activity of NF-κB has been implicated as an important aspect of many cancer cells, but mechanisms associated with this activity are poorly understood. An inducible kinase, IKK-i/IKKε, related to the catalytic forms of the IκB kinase, has been studied as an anti-viral, innate immune regulator through its ability to control the activity of the transcription factors IRF-3 and IRF-7. Here, we demonstrate that IKK-i/IKKε is expressed in a number of cancer cells and is involved in regulating NF-κB activity through its ability to control basal/constitutive, but not cytokine-induced, p65/RelA phosphorylation at Ser-536, a modification proposed to contribute to the transactivation function of NF-κB. Knockdown of IKK-i/IKKε or expression of a S536A mutant form of p65 suppresses HeLa cell proliferation. The data indicate a role for IKK-i/IKKε in controlling proliferation of certain cancer cells through regulation of constitutive NF-κB activity.

Original languageEnglish (US)
Pages (from-to)26976-26984
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number37
DOIs
StatePublished - Sep 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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