ABSTRACT
The ski oncogene induces muscle differentiation in otherwise nonmyogenic quail embryo cells (C. Colmenares and E. Stavnezer, Cell 59:293-303, 1989). Here we report that v-ski induces both MyoD and myogenin expression, suggesting that activation of these muscle regulatory genes may be a critical step in ski-induced myogenesis. We also describe a transformation-defective mutant of v-ski (tdM5i) that fails to induce myotube formation, although it induces the expression of many muscle-specific genes, including the MyoD and myogenin genes. Therefore, if activation of MyoD and myogenin expression is a necessary component of the myogenic program triggered by ski, it is clearly insufficient to account for complete muscle differentiation.
Subject(s)
Muscle Proteins/genetics , Muscles/cytology , Oncogenes , Amino Acid Sequence , Animals , Cell Differentiation , Cell Division , Cells, Cultured , DNA-Binding Proteins/genetics , Embryo, Nonmammalian , Molecular Sequence Data , Muscles/metabolism , Mutagenesis, Site-Directed , MyoD Protein , Myogenin , Quail , Trans-Activators/geneticsABSTRACT
The Sloan-Kettering viruses (SKVs) are a group of transforming retroviruses that were isolated from chicken embryo cells which had been infected with the avian leukosis virus transformation-defective Bratislava 77 (tdB77). Each of the SKV isolates was shown to contain multiple genomes of different sizes indicating the presence of several viruses in addition to tdB77. To identify and characterize the putative transforming gene(s) of the SKVs, we used hybridization selection to isolate the fraction of a representative cDNA which was SKV specific. Both solution and blot hybridization studies with viral RNAs showed that the specific probe contained a sequence, ski, that was at least partially held in common by the multiple SKV genomes. This conclusion was confirmed by the observation that a molecularly cloned ski probe also hybridized to each of the multiple SKV genomes. Southern blots of chicken DNA revealed homologs of ski (c-ski) which were not associated with endogenous viral loci. Results showing that c-ski was expressed in polyadenylated cytoplasmic RNA of uninfected chicken cells indicated that it is a functional gene. Other data showed that c-ski was conserved in avian and mammalian evolution, suggesting a functional role for the gene in species other than chickens. Using ski cDNA in solution hybridizations with viral RNAs and in Southern blot hybridization with cloned retroviral oncogenes, we did not detect any relationship between ski and any of 15 previously identified oncogenes.
