The transcription activation domains of v-Myc and VP16 interact with common factors required for cellular transformation and proliferation.
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.
Min
S
S
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392.
Crider-Miller
S J
SJ
Taparowsky
E J
EJ
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D015342:DNA Probes; D004926:Escherichia coli; D005786:Gene Expression Regulation; D016259:Genes, myc; D017405:Herpes Simplex Virus Protein Vmw65 / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D017570:MyoD Protein / Q000737:chemistry / Q000502:physiology*; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D016274:Oncogene Protein p55(v-myc) / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018139:Simplexvirus / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis*
D015342:DNA Probes; D017405:Herpes Simplex Virus Protein Vmw65; D017570:MyoD Protein; D016274:Oncogene Protein p55(v-myc); D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D015689:Oncogene Protein p21(ras)