Cell cycle regulation of human diploid fibroblasts: possible mechanisms of platelet-derived growth factor

Cell-cycle regulation of human diploid fibroblasts (HDF) is located in the proximal half of G1, designated G1-pm (G1-postmitosis). In order to traverse this subphase, cells require serum factors or PDGF. However, when cells have traversed into the distal half of G1, designated G1-ps (G1-pre-DNA synthesis), they become independent of serum or PDGF and progress through the remainder of the cell cycle at an invariable rate. From this, it follows that a specific G1-pm block can be induced by serum depletion. A similar G1-pm block could also be induced by a moderate inhibition of overall protein synthesis following treatment with CHM. Even this block could be prevented by the addition of PDGF, suggesting that a high level of protein synthesis in itself is not necessary for sustaining cell-cycle traverse. Nevertheless, a critical accumulation of some specific proteins might be required for the G1-pm/G1-ps-transition. However, the underlying mechanisms of modulation of the accumulation of such proteins by PDGF must involve alternative regulatory events (e.g., gene expression, protein stabilization) rather than protein synthesis. Among the possible cell cycle-regulatory proteins, the present study focused on 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. This enzyme is regulated by various kinds of control mechanisms and regulates the biosynthesis of sterols and nonsterol isoprenes, some of which are proposed to be necessary for mammalian cell growth (Brown and Goldstein, 1980). The present results suggest that regulation of HMG CoA reductase may be involved in the control of the G1-pm/G1-ps-progression in HDF.