CELL-CYCLE DEPENDENT REGULATION OF CDC2 MESSENGER-RNA IN MOUSE FIBROBLASTS - REQUIREMENT OF PROTEIN-SYNTHESIS AND OF CONTINUED MITOGENIC STIMULATION

In the chemically transformed mouse fibroblasts (BP-A31) placed in a serum-free medium, the cdc2 mRNA content decreases in parallel with the cessation of [H-3]thymidine incorporation. Extinction of the cdc2 gene expression is also observed in BP-A31 cells overexpressing the human c-myc oncogene. At quiescence, the cdc2 gene expression can be reinduced with serum or with other mitogens such as insulin or 12-O-tetradecanoyl phorbol 13-acetate (TPA). The kinetics of induction is characterized by a lag period which differs according to the mitogen used and reflects the length of the G1 phase (4-6 h with insulin or serum, 9-12 h with TPA). The cdc2 mRNA accumulation is prevented when protein synthesis is blocked with cycloheximide, also if the drug is added at a time when the synthesis of cdc2 mRNA is already under way. Similarly, removal of the mitogen leads to a cessation of the cdc2 mRNA accumulation. These results suggest that the increased expression of the cdc2 gene is mediated by (a) short-lived, growth factor-regulated protein(s).