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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adenovirus E1A Proteins / genetics
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Adenovirus E1A Proteins / physiology
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Amino Acid Sequence
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Ataxia Telangiectasia Mutated Proteins
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Carrier Proteins*
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Cell Cycle Proteins*
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / pathology
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Conserved Sequence
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DNA, Complementary / isolation & purification
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DNA-Binding Proteins*
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E2F Transcription Factors
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E2F1 Transcription Factor
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Evolution, Molecular
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Genes, Dominant
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HeLa Cells
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Humans
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Oligonucleotides, Antisense / pharmacology
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Phosphatidylinositol 3-Kinases / chemistry
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Protein Binding
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Protein Serine-Threonine Kinases*
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Proteins / physiology*
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Proto-Oncogene Proteins c-myc / physiology*
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors / physiology*
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Tumor Suppressor Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Adenovirus E1A Proteins
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Carrier Proteins
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Cell Cycle Proteins
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DNA, Complementary
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DNA-Binding Proteins
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E2F Transcription Factors
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E2F1 Transcription Factor
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E2F1 protein, human
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Nuclear Proteins
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Oligonucleotides, Antisense
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Proteins
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Proto-Oncogene Proteins c-myc
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Retinoblastoma-Binding Protein 1
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Transcription Factor DP1
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Transcription Factors
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Tumor Suppressor Proteins
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transformation-transcription domain-associated protein
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases