Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetyltransferases / metabolism*
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
-
Basic-Leucine Zipper Transcription Factors
-
Carrier Proteins / metabolism
-
Catalytic Domain
-
Cell Cycle Proteins
-
Cell Line
-
Cell Transformation, Neoplastic
-
DNA-Binding Proteins / metabolism
-
Dimerization
-
Genes, Essential / genetics
-
Genes, Essential / physiology
-
HeLa Cells
-
Histone Acetyltransferases
-
Histone Deacetylases / metabolism
-
Humans
-
Models, Biological
-
Nuclear Proteins / metabolism*
-
Precipitin Tests
-
Protein Binding
-
Proto-Oncogene Proteins c-myc / antagonists & inhibitors
-
Proto-Oncogene Proteins c-myc / chemistry
-
Proto-Oncogene Proteins c-myc / genetics
-
Proto-Oncogene Proteins c-myc / metabolism*
-
Rats
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Repressor Proteins*
-
Saccharomyces cerevisiae Proteins*
-
Trans-Activators / chemistry
-
Trans-Activators / genetics
-
Trans-Activators / metabolism*
-
Transcription Factors*
-
p300-CBP Transcription Factors
Substances
-
Adaptor Proteins, Signal Transducing
-
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
-
Basic-Leucine Zipper Transcription Factors
-
Carrier Proteins
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
MAX protein, human
-
MXD1 protein, human
-
Max protein, rat
-
Myc associated factor X
-
Nuclear Proteins
-
Proto-Oncogene Proteins c-myc
-
Recombinant Fusion Proteins
-
Repressor Proteins
-
Saccharomyces cerevisiae Proteins
-
Trans-Activators
-
Transcription Factors
-
transformation-transcription domain-associated protein
-
Acetyltransferases
-
Histone Acetyltransferases
-
KAT2A protein, human
-
p300-CBP Transcription Factors
-
p300-CBP-associated factor
-
Histone Deacetylases