Related Experiment Video
Updated: Aug 21, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B
Josef Anrather1, Gianfranco Racchumi, Costantino Iadecola
1Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA. joa@med.cornell.edu
Abstract:
Phosphorylation of nuclear factor-kappa B (NF-kappa B) subunits emerges as a mechanism by which transcriptional activity of nuclear NF-kappa B complexes is regulated in an inhibitor kappa B-independent fashion. As the main transactivator, the p65 subunit of NF-kappa B has an outstanding position in the hierarchy of NF-kappa B 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 kappa B-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.
More Related Videos
Related Concept Videos
Co-activators and Co-repressors
Co-activators and Co-repressors
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Eukaryotic Transcription Activators
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
General Transcription Factors
Transcription Factors

