The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins

Cell. 1998 Aug 7;94(3):363-74. doi: 10.1016/s0092-8674(00)81479-8.

Abstract

The c-Myc and E2F transcription factors are among the most potent regulators of cell cycle progression in higher eukaryotes. This report describes the isolation of a novel, highly conserved 434 kDa protein, designated TRRAP, which interacts specifically with the c-Myc N terminus and has homology to the ATM/PI3-kinase family. TRRAP also interacts specifically with the E2F-1 transactivation domain. Expression of transdominant mutants of the TRRAP protein or antisense RNA blocks c-Myc- and E1A-mediated oncogenic transformation. These data suggest that TRRAP is an essential cofactor for both the c-Myc and E1A/E2F oncogenic transcription factor pathways.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / physiology
  • Amino Acid Sequence
  • Ataxia Telangiectasia Mutated Proteins
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Conserved Sequence
  • DNA, Complementary / isolation & purification
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Evolution, Molecular
  • Genes, Dominant
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Oligonucleotides, Antisense / pharmacology
  • Phosphatidylinositol 3-Kinases / chemistry
  • Protein Binding
  • Protein-Serine-Threonine Kinases*
  • Proteins / physiology*
  • Proto-Oncogene Proteins c-myc / physiology*
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / physiology*
  • Tumor Suppressor Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Adenovirus E1A Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Proteins
  • Proto-Oncogene Proteins c-myc
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Proteins
  • transformation-transcription domain-associated protein
  • Phosphatidylinositol 3-Kinases
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/AF076974