Structure-Function Analysis of the v-Myc Oncoprotein

The biological activities of the v-Myc oncoprotein, including cellular transformation, transcription regulation and apoptosis, depend on the integrity of the v-Myc amino terminus. Analysis of this region using deletion mutagenesis has yielded interesting results. In addition to further defining regions of the amino terminus required for transcriptional activation, a potential inhibitory region of v-Myc transactivation has been identified. New data suggest that the ability of individual deletions to function in transcription as says is not due to different levels of protein expression, supporting an actual difference in the transcriptional abilities of the novel proteins generated by these deletions. The identification and characterization of a protein that specifically interacts with a region of the v- Myc amino terminus has suggested another form of regulation of the v-Myc oncoprotein. This protein, termed OS-9, interacts with a highly conserved and functionally important region of v- Myc called Myc Homology Region II. While no effect of OS-9 has been observed on cellular transformation mediated by v-Myc, OS-9 does impact v-Myc transcriptional activation. Transcriptional activity of the v-Myc activation domain is reduced by nearly 75 when OS-9 is overexpressed in cells. This repression does not extend to other activators -- for example, the activation domain of MyoD is unaffected by OS-9. These data point to the interaction of OS-9 with Mvc as being important in regulating the acivities of v-Mvc as a transcription factor.