Expression of p60v-src in Saccharomyces cerevisiae results in elevation of p34CDC28 kinase activity and release of the dependence of DNA replication on mitosis.
Expression of the oncogenic protein tyrosine kinase p60v-src in the yeast Saccharomyces cerevisiae has been shown to result in rapid cell death (J. S. Brugge, G. Jarosik, J. Andersen, A. Queral-Lustig, M. Fedor-Chaiken, and J. R. Broach, Mol. Cell. Biol. 7:2180-2187, 1987). Work described here demonstrates that v-Src expression results in accumulation of large-budded cells and a nuclear division block without blocking cytokinesis. Flow-cytometric analysis indicates that the DNA content of these cells is elevated beyond the G2 DNA content, and genetic studies indicate that v-Src expression causes aneuploidy. The activity of Cdc28 kinase, which controls the G1/S and G2/M transitions in S. cerevisiae, increases during galactose induction in a Src+ strain but not in an isogenic Src- strain. These observations indicate that v-Src expression disrupts p34CDC28 kinase regulation, allowing DNA replication to proceed in the absence of a prior mitotic event.
Boschelli
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Department of Biochemistry, Wayne State University School of Medicine, Detroit, Michigan 48201.
D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism*; D002453:Cell Cycle; D004261:DNA Replication; D015966:Gene Expression Regulation, Fungal; D016391:Genes, src; D008938:Mitosis; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D019000:Phosphotyrosine; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology; D014170:Transformation, Genetic; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D019000:Phosphotyrosine; D014443:Tyrosine; D015688:Oncogene Protein pp60(v-src); D017489:CDC28 Protein Kinase, S cerevisiae