Control of late G0/G1 progression and protein modification by SmC/IGF I

Somatomedin C/insulin-like growth factor I (SmC/IGF I) mediates traverse of late G0/G1 in density-arrested BALB/c-3T3 cells from a distinct growth arrest point in mid-G0/G1 (the V point) to the initiation of DNA synthesis. As a prelude to future studies aimed at defining the mechanism of action of SmC/IGF I, we investigated the level (e.g., transcriptional, translational) at which SmC/IGF I modulates V to S traverse. The post-V point progression of cells arrested at the V point by amino acid starvation and released into amino acid-replenished medium containing SmC/IGF I, insulin, or platelet-poor plasma (PPP) did not require either mRNA synthesis or an increase in the overall level of protein synthesis. Although two-dimensional gel analysis of proteins prepared from SmC/IGF I-treated cells did not reveal any preferentially synthesized proteins, several SmC/IGF I-induced protein modifications, which result in an increase in isoelectric point (pI) and occur in the absence of mRNA synthesis, were evident. These findings suggest that SmC/IGF I modulates late G0/G1 progression by a posttranscriptional process that may involve protein modification.