The ATM-related domain of TRRAP is required for histone acetyltransferase recruitment and Myc-dependent oncogenesis

Genes Dev. 2001 Jul 1;15(13):1619-24. doi: 10.1101/gad.900101.

Abstract

The ATM-related TRRAP protein is a component of several different histone acetyltransferase (HAT) complexes but lacks the kinase activity characteristic of other ATM family members. We identified a novel function for this evolutionarily conserved domain in its requirement for the assembly of a functional HAT complex. Ectopic expression of TRRAP protein with a mutation in the ATM-related domain inhibits Myc-mediated oncogenic transformation. The Myc-binding region of TRRAP maps to a separable domain, and ectopic expression of this domain inhibits cell growth. These findings demonstrate that the ATM-related domain of TRRAP forms a structural core for the assembly and recruitment of HAT complexes by transcriptional activators.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism*
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Binding Sites
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Cell Line
  • Cell Transformation, Neoplastic*
  • DNA-Binding Proteins
  • Histone Acetyltransferases
  • Histones / metabolism
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators / metabolism
  • Transcription Factors*
  • Tumor Suppressor Proteins
  • p300-CBP Transcription Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • SUPT3H protein, human
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Proteins
  • transformation-transcription domain-associated protein
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases