CHARACTERIZATION OF LATE RESPONSE GENES SEQUENTIALLY EXPRESSED DURINGRENEWED GROWTH OF FIBROBLASTIC CELLS

Many proto-oncogenes are rapidly and transiently activated during the early stages of the cellular transition from a resting G0 state to the DNA synthesis (S) phase. To get better understanding of the gene comp lexity involved at later stages, we isolated, by cDNA cloning, and ide ntified 17 genes that are activated sequentially during the period of time from proto-oncogene expression to the onset of DNA synthesis in t he hamster CCL39 fibroblastic cell line. When protein synthesis is inh ibited, induced expression of these genes is unaffected for 10 of them , enhanced for four, in a fashion similar to the immediate-early respo nse genes, and inhibited for three, as observed for delayed early-resp onse genes. In addition to rhoG, a new member of the ras homolog gene family (Vincent et al., 1992), cDNA sequencing indicated that six of t hem correspond to cytoskeletal proteins (alpha-tubulin, vascular alpha -actin and skeletal gamma-actin), extracellular matrix protein (thromb ospondin), secreted protease (plasminogen activator inhibitor-1) and e nergy-linked transporter (mitochondrial proton/phosphate symporter). T his overall survey shows that numerous differentially regulated gene a ctivations are associated with the cell cycle progression, and suggest s that proteins involved in cellular reshaping participate actively in the control of cellular growth.