The goals of this revised Program Project renewal application are the same as in the original application, i.e. a collaborative effort to elucidate the mechanism(s) of cell cycle progression in mammalian cells. The revised application brings together three investigators with an established expertise in cell cycle research, each in different areas: Bruno Calabretta in gene expression, Antonio Giordano in the role of cyclins and cyclin-associated proteins, and Renato Baserga in the field of growth factors and their receptors. These areas are tightly related to each other, since cyclins and cyclin-associated proteins are involved in regulation of gene expression, and both are dependent upon environmental signals, among which growth factors are prominent. The purpose of this proposed project is to utilize the expertise of three different investigators to establish firm connections between the activation of growth factors receptors, and modulations of cyclins and associated proteins and the expression of growth regulated genes, leading eventually to cell growth.