The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins.
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.
McMahon
S B
SB
Department of Molecular Biology, Princeton University, New Jersey 08544-1014, USA.
Van Buskirk
H A
HA
Dugan
K A
KA
Copeland
T D
TD
Cole
M D
MD
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000502:physiology; D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D019143:Evolution, Molecular; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D017500:Adenovirus E1A Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C493753:E2F1 protein, human; C113829:transformation-transcription domain-associated protein; C576324:ATM protein, human