DISTINCT MECHANISMS CONTROL THE ACCUMULATION OF THE RB-RELATED P107 AND P130 PROTEINS DURING CELL-GROWTH

A variety of studies have demonstrated the critical role of the Rb/E2F pathway in the control of cell growth and have highlighted a complexi ty in the accumulation of both the E2F family proteins and the Rb fami ly of proteins. Whereas the Rb protein is found in both growing and qu iescent cells, the accumulation of p130 and p107 is tightly regulated with respect to the growth state of the cell. The p130 protein is foun d in quiescent cells but not in growing cells, whereas the inverse is true for the p107 protein, Control of p130 accumulation is posttranscr iptional, because p130 RNA is relatively constant in growing and quies cent cells. The disappearance of the p130 protein after stimulation of cell growth coincides with cyclin-dependent kinase-mediated phosphory lation and is blocked by inhibitors of the 26S proteasome. In contrast , the cell growth-dependent regulation of p107 expression reflects the transcriptional regulation of the p107 gene. Similar to several other growth-regulated genes, the control of p107 expression is largely the result of E2F-dependent repression in quiescent cells. These experime nts thus demonstrate a control of Rb family member expression mediated through distinct mechanisms of both transcriptional and posttranslati onal control and also suggest an intimate relationship in which p130 c ontrols the expression of p107.