The alpha-helical FXXPhiPhi motif in p53: TAF interaction and discrimination by MDM2

Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14801-6. doi: 10.1073/pnas.96.26.14801.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Protein Binding
  • Protein Structure, Secondary
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • TATA-Binding Protein Associated Factors*
  • Trans-Activators / metabolism*
  • Transcription Factor TFIID*
  • Transcriptional Activation*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*


  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • TAF9 protein, human
  • TATA-Binding Protein Associated Factors
  • Trans-Activators
  • Transcription Factor TFIID
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2