Thr(435) phosphorylation regulates RelA (p65) NF-kappa B subunit transactivation (2010)

Author(s): O'Shea JM, Perkins ND

    Abstract: Phosphorylation of the RelA (p65) NF-kappa B (nuclear factor kappa B) subunit has been previously shown to Modulate its ability to induce or repress transcription. In the present study we have investigated the consequences of Thr(435) phosphorylation within the C-terminal transactivation domain of RelA. We confirm that Thr(435) is phosphorylated in cells and is induced by TNF alpha (tumour necrosis factor alpha) treatment. Mutational analysis of this site revealed gene-specific effects oil transcription, with a T435D phosphomimetric 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 historic acetylation associated with decreased recruitment of HDAC1 (histone deacetylase 1). Moreover. Mutation of this Site disrupted RelA interaction with in vitro. Thr(435) phosphorylation of promoter-bound RelA was also detected at NF-kappa B larger genes following TNF alpha treatment ill wild-type Mouse embryonic fibroblasts. Phosphorylation at this site therefore provides all additional mechanism through which the specificity of NF-kappa B transcriptional activity can be modulated in cells.

      • Date: 15-12-2009
      • Journal: Biochemical Journal
      • Volume: 426
      • Issue: 3
      • Pages: 345-354
      • Publisher: Portland Press Ltd.
      • Publication type: Article
      • Bibliographic status: Published

      Professor Neil Perkins
      Prof of Gene Exp & Signalling