title: TFIIB dephosphorylation links transcription inhibition with the p53-dependent DNA damage response.
abstract: The general transcription factor II B (TFIIB) plays a central role in both the assembly of the transcription complex at gene promoters and also in the events that lead to transcription initiation. TFIIB is phosphorylated at serine-65 at the promoters of several endogenous genes, and this modification is required to drive the formation of gene promoter-3' processing site contacts through the cleavage stimulation factor 3' (CstF 3')-processing complex. Here we demonstrate that TFIIB phosphorylation is dispensable for the transcription of genes activated by the p53 tumor suppressor. We find that the kinase activity of TFIIH is critical for the phosphorylation of TFIIB serine-65, but it is also dispensable for the transcriptional activation of p53-target genes. Moreover, we demonstrate that p53 directly interacts with CstF independent of TFIIB phosphorylation, providing an alternative route to the recruitment of 3'-processing complexes to the gene promoter. Finally, we show that DNA damage leads to a reduction in the level of phospho-ser65 TFIIB that leaves the p53 transcriptional response intact, but attenuates transcription at other genes. Our data reveal a mode of phospho-TFIIB-independent transcriptional regulation that prioritizes the transcription of p53-target genes during cellular stress.
authors.affiliation: Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.
authors.forename: Jayasha
authors.initials: J
authors.lastname: Shandilya
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wang
authors.forename: Stefan G E
authors.initials: SG
authors.lastname: Roberts
mesh_terms: D039241:Cleavage Stimulation Factor / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation / Q000502:physiology; D035581:Transcription Factor TFIIB / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D039241:Cleavage Stimulation Factor; C495901:TP53 protein, human; D035581:Transcription Factor TFIIB; D016159:Tumor Suppressor Protein p53