title: Structure of the Tfb1/p53 complex: Insights into the interaction between the p62/Tfb1 subunit of TFIIH and the activation domain of p53.
abstract: The interaction between the amino-terminal transactivation domain (TAD) of p53 and TFIIH is directly correlated with the ability of p53 to activate both transcription initiation and elongation. We have identified a region within the p53 TAD that specifically interacts with the pleckstrin homology (PH) domain of the p62 and Tfb1 subunits of human and yeast TFIIH. We have solved the 3D structure of a complex between the p53 TAD and the PH domain of Tfb1 by NMR spectroscopy. Our structure reveals that p53 forms a nine residue amphipathic alpha helix (residues 47-55) upon binding to Tfb1. In addition, we demonstrate that diphosphorylation of p53 at Ser46 and Thr55 leads to a significant enhancement in p53 binding to p62 and Tfb1. These results indicate that a phosphorylation cascade involving Ser46 and Thr55 of p53 could play an important role in the regulation of select p53 target genes.
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Lello
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Lisa M Miller
authors.initials: LMM
authors.lastname: Jenkins
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602.
authors.forename: Tamara N
authors.initials: TN
authors.lastname: Jones
authors.affiliation: Department of Chemistry, University of California, Irvine, California 92697.
authors.forename: Bao D
authors.initials: BD
authors.lastname: Nguyen
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hara
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Molecular Biochemistry of Hypertension, Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Dikeakos
authors.affiliation: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Ettore
authors.initials: E
authors.lastname: Appella
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Pascale
authors.initials: P
authors.lastname: Legault
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, Québec H3C 3J7, Canada. Electronic address: jg.omichinski@umontreal.ca.
authors.forename: James G
authors.initials: JG
authors.lastname: Omichinski
mesh_terms: D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D040681:Structural Homology, Protein; D051758:Transcription Factor TFIIH / Q000737:chemistry* / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C086993:TFB1 protein, S cerevisiae; D019473:Transcription Factors, TFII; D016159:Tumor Suppressor Protein p53; D051758:Transcription Factor TFIIH