Expression of C-MYC, C-FOS and C-JUN Proto-Oncogenes During Muscle Differentiation in Vitro

Abstract

Proto-oncogenes have been shown to code for growth factors, cell surface receptors, membrane proteins, phosphokinases and nuclear proteins. Most of these oncoproteins appear to be part of signalling pathways which elicit or transduce growth regulatory signals from the cell surface to the cell nucleus. Abnormal expression of one or several proto-oncogenes may cause abnormal cell growth. Among the nuclear proteins coded by proto-oncogenes (c-onc) are c-Myc, c-Fos and c-Jun. These proteins have the potential to regulate other genes by interacting directly or indirectly with DNA, thereby influencing gene transcription. The c-fos gene encodes a nuclear phosphoprotein with a half-life of approximately 20 min. Via conserved regions rich in leucine (leucine zipers) the c-Fos protein forms a heterodimer complex with the transcription factor c-Jun/AP-1. The Fos/Jun complex has the ability to bind to regulatory elements of other genes. Both the c-Fos and c-Jun proteins have been found to be families of related proteins which can form hetero- and homodimers with varying affinities for a specific DNA sequence (TGACTCA). The c-myc gene encodes a nuclear phosphoprotein of 58–66kD and similar to the c-Fos and c-Jun proteins it has a short half-life. The c-fos, c-jun, and c-myc genes are activated when quiescent cells are stimulated to proliferate by the addition of growth factors. This event is believed to be important in linking mytogen-induced short term physiological changes to altered patterns of gene expression, cell growth and proliferation.