Cell cycle and growth control

Increments in our understanding of eukaryotic cell cycle and growth control have accrued steadily during the past several decades.Landmark contributions initially involved subdivision of the cell cycle into four discrete periods-G1 (postmitotic presynthetic), S-phase (DNA replication), G2 (postsynthetic premitotic), and mitotic.Also early on, the requirements of transcription and translation for the onset of DNA replication and mitotic division were established by elegant studies using inhibitors of RNA and protein synthesis.The identification of growth factors and growth factor receptors that mediate competency for proliferation and progression through the cell cycle past a GI restriction point provided the basis for pursuit of proliferation-related regulatory mechanisms from both conceptual and experimental standpoints.The identification of proteins that exhibit activity which is preferentially or completely restricted to specific periods of the cell cycle and the characterization of the genes encoding these cell cycle-regulated proteins have been instrumental in focusing on defined components of control mechanisms operative during proliferation.It was the identification and characterization of a series of cell cycle mutants in yeast which yielded valuable insight into growth regulatory proteins and factors that modulate activities of these cell cycle regulatory molecules (e.g., cyclins and cyclin-related kinases).Equally important for our understanding of cell cycle regulatory mechanisms has been increased awareness of the multiple roles of oncogenes and tumor suppressors, many of which encode growth factors, growth factor receptors or molecules which mediate growth factor activity.The past several years have been catalytic.We are beginning to unravel the complexity of signaling mechanisms which integrate and coordinate transcriptional and post transcriptional control of gene expression requisite for proliferation.