The ATM-related domain of TRRAP is required for histone acetyltransferase recruitment and Myc-dependent oncogenesis.
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.
Park
J
J
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544-1014, USA.
Kunjibettu
S
S
McMahon
S B
SB
Cole
M D
MD
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D048868:Adaptor Proteins, Signal Transducing; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C115819:SUPT3H protein, human; C113829:transformation-transcription domain-associated protein; C576324:ATM protein, human