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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Acetyltransferases / metabolism*
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Adaptor Proteins, Signal Transducing
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Binding Sites
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cell Line
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Cell Transformation, Neoplastic*
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DNA-Binding Proteins
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Histone Acetyltransferases
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Histones / metabolism
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Humans
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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Rats
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae Proteins*
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Trans-Activators / metabolism
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Transcription Factors*
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Tumor Suppressor Proteins
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p300-CBP Transcription Factors
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Histones
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Nuclear Proteins
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Proto-Oncogene Proteins c-myc
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Recombinant Fusion Proteins
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SUPT3H protein, human
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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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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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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ATM protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases