The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc.
The c-Myc protein functions as a transcription factor to facilitate oncogenic transformation; however, the biochemical and genetic pathways leading to transformation remain undefined. We demonstrate here that the recently described c-Myc cofactor TRRAP recruits histone acetylase activity, which is catalyzed by the human GCN5 protein. Since c-Myc function is inhibited by recruitment of histone deacetylase activity through Mad family proteins, these opposing biochemical activities are likely to be responsible for the antagonistic biological effects of c-Myc and Mad on target genes and ultimately on cellular transformation.
McMahon
S B
SB
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Wood
M A
MA
Cole
M D
MD
D000123:Acetyltransferases / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins / Q000378:metabolism; D020134:Catalytic Domain; D018797:Cell Cycle Proteins; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D020043:Genes, Essential / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C499330:MAX protein, human; C079439:MXD1 protein, human; C499329:Max protein, rat; C067850:Myc associated factor X; C113829:transformation-transcription domain-associated protein; C501179:KAT2A protein, human