We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Thr435 phosphorylation regulates RelA (p65) NF-kappaB subunit transactivation.

The Biochemical journal | Feb 24, 2010

Phosphorylation of the RelA (p65) NF-kappaB (nuclear factor kappaB) subunit has been previously shown to modulate its ability to induce or repress transcription. In the present study we have investigated the consequences of Thr435 phosphorylation within the C-terminal transactivation domain of RelA. We confirm that Thr435 is phosphorylated in cells and is induced by TNFalpha (tumour necrosis factor alpha) treatment. Mutational analysis of this site revealed gene-specific effects on transcription, with a T435D phosphomimetic mutant significantly enhancing Cxcl2 (CXC chemokine ligand 2) mRNA levels in reconstituted Rela-/- mouse embryonic fibroblasts. Chromatin immunoprecipitation analysis revealed that this mutation results in enhanced levels of histone acetylation associated with decreased recruitment of HDAC1 (histone deacetylase 1). Moreover, mutation of this site disrupted RelA interaction with HDAC1 in vitro. Thr435 phosphorylation of promoter-bound RelA was also detected at NF-kappaB target genes following TNFalpha treatment in wild-type mouse embryonic fibroblasts. Phosphorylation at this site therefore provides an additional mechanism through which the specificity of NF-kappaB transcriptional activity can be modulated in cells.

Pubmed ID: 20001970 RIS Download

Mesh terms: Animals | Blotting, Western | Cell Line | Cell Line, Tumor | Chemokine CXCL2 | Gene Expression Regulation | Histone Deacetylase 1 | Humans | Immunoprecipitation | Mice | Mice, Knockout | Mutation | Oxazoles | Phosphoprotein Phosphatases | Phosphorylation | Protein Binding | Reverse Transcriptase Polymerase Chain Reaction | Threonine | Transcription Factor RelA | Transcriptional Activation | Tumor Necrosis Factor-alpha

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants

  • Agency: Cancer Research UK, Id: C1443/A4201
  • Agency: Wellcome Trust, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.