E2F1 and c-Myc in cell growth and death

Abstract

Cell cycle machinery controls not only cell growth but also cell survival and death. For example, overexpression of c-Myc or E2F1, which are involved in G1/S transition, causes apoptosis under certain conditions. Furthermore, endogenous E2F1 also participates in apoptosis, as evidenced by the defect of apoptosis in E2F1-deficient mice. Candidate molecules that mediate c-Myc- and E2F1-enhanced apoptosis include p14/p19ARF, ornithine decarboxylase and lactate dehydrogenase-A (for c-Myc) as well as p14/p19ARF, p73, Apaf-1 and caspase-3 (for E2F1). c-Myc also activates the CD95/Fas-FADD-mediated death signal. c-Myc and E2F1 inhibit NF-kappaB activities induced by TNFalpha or reactive oxygen species. Therefore, c-Myc and E2F1 regulate cell growth and death not only by inducing transcription but also by modulating signal transduction pathways.