title: The alpha-helical FXXPhiPhi motif in p53: TAF interaction and discrimination by MDM2.
abstract: Transcriptional activation domains share little sequence homology and generally lack folded structures in the absence of their targets, aspects that have rendered activation domains difficult to characterize. Here, a combination of biochemical and nuclear magnetic resonance experiments demonstrates that the activation domain of the tumor suppressor p53 has an FXXPhiPhi motif (F, Phe; X, any amino acids; Phi, hydrophobic residues) that folds into an alpha-helix upon binding to one of its targets, hTAF(II)31 (a human TFIID TATA box-binding protein-associated factor). MDM2, the cellular attenuator of p53, discriminates the FXXPhiPhi motif of p53 from those of NF-kappaB p65 and VP16 and specifically inhibits p53 activity. Our studies support the notion that the FXXPhiPhi sequence is a general alpha-helical recognition motif for hTAF(II)31 and provide insights into the mechanistic basis for regulation of p53 function.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, MA 02138, USA.
authors.forename: M
authors.initials: M
authors.lastname: Uesugi
authors.forename: G L
authors.initials: GL
authors.lastname: Verdine
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators / Q000378:metabolism*; D035362:Transcription Factor TFIID; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C106849:TAF9 protein, human; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2