Role of Fos Proteins in the Induction of Transformation and DNA Synthesis
This chapter addresses the role of Fos proteins and activator protein (AP-1) complexes in cell proliferation and, more specifically, in GO/G1-to-S progression. The most crucial region of Fos for the induction of transformation lies between amino acids 111 and 220. The transformation of muscle cells by Fos leads to a block of myogenesis, apparently by an inhibition of myoD expression. The oncogenic potential of fos genes seems, however, to be restricted to connective tissue cells, since the malignant transformation of other cell types in vitro has not been achieved to date. A number of cell lines stably expressing Fos-estrogen receptor fusion proteins have been isolated and analyzed for hormone-dependent transformation and transregulation. During prenatal development the c-fos gene is expressed at high levels specifically in the cells of the cartilaginous growth zones of the bones, suggesting a role in cell proliferation.