c-Myc in the control of cell proliferation and embryonic development

This chapter reviews recent knowledge on the cell cycle regulation of c-Myc expression and c-Myc activity, as well as the structural features of the c-Myc protein that give new insights into the understanding of c-Myc function during the cell cycle and embryonic development. C-myc was the first nuclear proto-oncogene discovered and has been the subject of intense investigation during the past 16 years. The initial property attributed to c-Myc was its ability to transform normal cultured cells, but a great deal of evidence since then has indicated that this proto-oncogene is involved in a variety of different cellular processes—such as proliferation, differentiation, and apoptosis. The current focus of investigation into c-Myc is, therefore, primarily concerned with deciphering the way one gene can both participate in and discriminate between these seemingly divergent activities. Embryonic development requires cellular multiplication coupled to diversification of the genetic program, and therefore additional levels of control are required to provide a tight coordination between proliferation and differentiation. The biochemical analysis of c-Myc activity has been hampered by the extreme difficulty in obtaining a soluble form of the purified full-length protein. The chapter also discusses cell proliferation and c-Myc as a transcription factor. The majority of studies concerning c-Myc expression in adult tissues or embryos are related to the production of mRNA, although gene expression does not always strictly correlate with the temporal pattern and level of protein expression during development. While proliferating cells exhibit stable c-Myc RNA levels and abrupt changes in c-Myc expression are often observed during exit from the cell cycle, because cells undergo terminal differentiation. During the past decade it has become increasingly apparent that programmed cell death, or apoptosis, is a fundamental process affecting both growth and development. © 1996 Academic Press Inc.