cis-Acting Element-specific Transcriptional Activity of Differentially Phosphorylated Nuclear Factor-κB*

Phosphorylation of nuclear factor-κB (NF-κB) subunits emerges as a mechanism by which transcriptional activity of nuclear NF-κB complexes is regulated in an inhibitor κB-independent fashion. As the main transactivator, the p65 subunit of NF-κB has an outstanding position in the hierarchy of NF-κB proteins. p65 is a multiply phosphorylated protein with phosphorylation sites in the C-terminal transactivation domain and the N-terminal Rel homology domain (RHD). In this study, we describe two previously non-reported phospho-acceptor sites within the p65 RHD. We show that differential phosphorylation of serine residues within the RHD modulates transcriptional activity in a cis-acting element and promoter-specific context, thus leading to a phosphorylation state-dependent gene expression profile. RelA-/- mouse embryonic fibroblasts reconstituted with wild-type p65 or p65 phosphorylation-deficient mutants showed a distinctive expression profile of synthetic κB-dependent reporters as well as endogenous genes. Hypophosphorylated p65 did not display cis-acting element-specific changes in DNA binding or dimerization behavior. This study shows for the first time that site-specific phosphorylation can target a transcription factor to a particular subset of genes.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-01-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.M409344200PMID 15516339
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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