Multiple direct interactions of TBP with the MYC oncoprotein

Nat Struct Mol Biol. 2019 Nov;26(11):1035-1043. doi: 10.1038/s41594-019-0321-z. Epub 2019 Nov 4.


Transcription factor c-MYC is a potent oncoprotein; however, the mechanism of transcriptional regulation via MYC-protein interactions remains poorly understood. The TATA-binding protein (TBP) is an essential component of the transcription initiation complex TFIID and is required for gene expression. We identify two discrete regions mediating MYC-TBP interactions using structural, biochemical and cellular approaches. A 2.4 -Å resolution crystal structure reveals that human MYC amino acids 98-111 interact with TBP in the presence of the amino-terminal domain 1 of TBP-associated factor 1 (TAF1TAND1). Using biochemical approaches, we have shown that MYC amino acids 115-124 also interact with TBP independently of TAF1TAND1. Modeling reveals that this region of MYC resembles a TBP anchor motif found in factors that regulate TBP promoter loading. Site-specific MYC mutants that abrogate MYC-TBP interaction compromise MYC activity. We propose that MYC-TBP interactions propagate transcription by modulating the energetic landscape of transcription initiation complex assembly.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / metabolism
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Maps*
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / metabolism*
  • TATA-Binding Protein Associated Factors / chemistry
  • TATA-Binding Protein Associated Factors / metabolism
  • TATA-Box Binding Protein / chemistry
  • TATA-Box Binding Protein / metabolism*
  • Transcription Factor TFIID / chemistry
  • Transcription Factor TFIID / metabolism


  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • TATA-Binding Protein Associated Factors
  • TATA-Box Binding Protein
  • Transcription Factor TFIID
  • Histone Acetyltransferases
  • TATA-binding protein associated factor 250 kDa