v-jun oncogene prevents terminal differentiation and suppresses muscle-specific gene expression in ASV-17-infected muscle cells.
Infection of replicating quail myoblasts with avian sarcoma virus 17 (ASV-17) results in the inhibition of terminal differentiation into multinucleated myotubes and in the acquisition of anchorage-independent proliferation. Expression of v-jun, the ASV-17 oncogene, concomitantly leads to the accumulation of the gag-jun polyprotein P65 in the nucleus and to the lack of expression of typical differentiation-specific genes such as myosin heavy chain (MHC) and alpha-actinin. Surprisingly, expression of desmin, the muscle-specific subunit of intermediate filaments, is conserved in ASV-17-transformed myoblasts. Analysis of clonal strains of transformed myoblasts suggests that (i) suppression of morphological and biochemical differentiation depends on the absence of muscle-specific gene transcripts; (ii) inhibition of muscle differentiation by v-jun does not depend on the transcriptional silencing of MyoD, a muscle-specific regulatory gene; (iii) expression of desmin is compatible with proliferation of ASV-17-transformed cells and is independent of v-jun and MyoD levels of expression. The present data suggest that nuclear localization of v-jun prevents terminal differentiation in myoblasts and selectively down-regulates muscle-specific genes in terminally differentiated myotubes. In this respect, the behaviour of v-jun is quite different from that of v-myc, thus suggesting that these two oncogenes, although both encoding nuclear proteins, may have different mechanisms of action.
Dipartimento di Biologia Cellulare e dello Sviluppo, Università di Roma La Sapienza, Italy.
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D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division; D002472:Cell Transformation, Viral / Q000235:genetics*; D016758:Genes, jun / Q000502:physiology*; D009132:Muscles / Q000166:cytology* / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure; D011784:Quail