The amino terminus of the avian myelocytomatosis virus MC29 v-Myc oncoprotein 
contains sequences that are essential for cellular transformation (S. Farina, et 
al. J. Virol., 66: 2698-2708, 1992; S. Min and E. J. Taparowsky. Oncogene, 
7:1531-1540, 1992) and for the ability to activate gene transcription (S. Min 
and E. J. Taparowsky. Oncogene, 7:1531-1540, 1992). To investigate the molecular 
interactions that mediate these v-Myc-associated activities, we performed 
competition assays in which various regions of the v-Myc amino terminal 
transcription activation domain (TAD) were examined for their ability to inhibit 
transcription activation by v-Myc, VP16, and the myogenic regulatory factor 
MyoD. Overexpression of these transcriptional activators also was used to 
investigate whether Myc-interacting proteins were required for cellular 
transformation and cell proliferation events. Our results demonstrate that at 
least two distinct cellular activities interact with the v-Myc TAD and that it 
is the synergism between these activities that is required for v-Myc to function 
fully as a transcriptional activator. In addition, v-Myc activators squelch 
VP16- and MyoD-dependent transcription activation, suggesting that the v-Myc TAD 
interacts with a component of the general transcription machinery. In support of 
this observation, we found that overexpression of the v-Myc TAD inhibits 
ras-mediated cellular transformation as well as cell proliferation, underscoring 
the critical role these amino terminal Myc-interacting factors play in 
regulating the physiology of both normal and transformed cells.