The Essential Cofactor TRRAP Recruits the Histone Acetyltransferase hGCN5 to c-Myc

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.

ACKNOWLEDGMENTS

We are grateful to Shelley Berger and Nickolai Barlev of the Wistar Institute for generously providing antibodies to human GCN5 and to Elizabeth Moran for advice regarding histone acetylation assays. We also thank Penny Rushton for excellent technical assistance.

S.B.M. is a Special Fellow of the Leukemia Society of America.