Structure-Function Analysis of the v-Myc Oncoprotein.
Abstract
Oncoproteins of the Myc family are important regulators or cellular proliferation, differentiation, transformation, and apoptosis. Overwhelming evidence suggests the transcription activation domain, or TAD, of Myc is responsible for mediating all of Myc's functions in vivo. In an attempt to more clearly define regions of the amino terminus important to Myc activity, deletion mutagenesis of the v-Myc TAD was performed. Examination of the truncated Myc proteins by reporter gene assays identified a region within the v-Myc amino terminus that acts as a negative regulatory domain. A yeast two-hybrid screen also was performed using a highly conserved domain of the v-Myc TAD called Myc homology region II, or MHR II. Analysis of the 22 positive clones obtained indicated that 8 represented overlapping isolates of the cDNA encoding the OS-9 protein. In vitro binding experiments demonstrate OS-9 specifically interacts with regions of the v-Myc TAD that contain MHR II. To determine the functional consequences of the Myc/OS-9 interaction, OS-9 was overexpressed in cells. Interestingly, co-expression of OS-9 dramatically inhibits transactivation by Myc and enhances transcriptional repression by Myc. More importantly, expression of OS-9 slows the growth of cells stimulated to proliferate by v-Myc overexpression. These data indicate that OS-9 is a novel modulator of v-Myc transcriptional activity, and this modulation has important consequences to the growth of cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1998
- Accession Number
- ADA349601
Entities
People
- Deborah Echlin
Organizations
- Purdue Research Foundation