title: Activation of nuclear factor-kappaB-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of RelA/p65 on serine 529.
abstract: Nuclear factor-kappaB (NF-kappaB) is an essential transcription factor in the control of expression of genes involved in immune and inflammatory responses. In unstimulated cells, NF-kappaB complexes are sequestered in the cytoplasm through interactions with IkappaBalpha and other IkappaB proteins. Extracellular stimuli that activate NF-kappaB, such as tumor necrosis factor alpha (TNFalpha), cause rapid phosphorylation of IkappaBalpha at serines 32 and 36. The inducible phosphorylation of IkappaBalpha is followed by its ubiquitination and degradation, allowing NF-kappaB complexes to translocate into the nucleus and to activate gene expression. Previously, it has been shown that TNFalpha as well as other stimuli also lead to the phosphorylation of the RelA/p65 subunit of NF-kappaB. In this report, we demonstrate that the TNFalpha-induced phosphorylation of the RelA/p65 subunit occurs on serine 529, which is in the C-terminal (TA1) transactivation domain. Accordingly, the TNFalpha-induced phosphorylation of Rel/p65 increases NF-kappaB transcriptional activity but does not affect nuclear translocation or DNA binding affinity.
authors.affiliation: Lineberger Comprehensive Cancer Center and Department of Biology, CB 7295, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.p6
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: A S
authors.initials: AS
authors.lastname: Baldwin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D012694:Serine