Figure 9.

 A schematic summary of the inhibitory activity of PSM-RB on G₁/S transition and S-phase progression. Cell cycle inhibitory effects observed in this study are depicted by the vertical T-bars. The lack of any effect is depicted by open circles. The solid arrows indicate an observed rescue of the negative effect. (R) Restriction point. PSM-RB inhibits S-phase entry and this is correlated with the inhibition of cyclin A expression. Three cdk inhibitors: p16ink4a, p21cip1, and p27kip1, each can also inhibit G₁/S transition. Unlike p16ink4a, PSM-RB does not interfere with the phosphorylation of p107 and p130. PSM-RB also inhibits DNA synthesis when it is expressed in cells that have traversed the G₁ restriction point. These post-R cells are not inhibited by the three cdk inhibitors tested. Overproduction of the SV40 T-Ag can overcome both the G₁/S and the S-phase inhibitory function of PSM-RB. Overproduction of cyclin E can overcome the G₁ block, induced by either p16ink4a or PSM-RB. However, overproduction of cyclin E cannot overcome the negative effect of PSM-RB on S-phase progression. These results suggest that unphosphorylated RB can interfere with DNA synthesis beyond the G₁-restriction point, and this negative function of RB does not appear to be mediated by the inhibition of the known G₁/S cyclin/cdk activities.