The ins and outs of RB: coupling gene expression to the cell cycle clock.

Extracellular growth-stimulatory and -inhibitory signals govern the subunit assembly and activity of G1 cyclin-dependent kinases (cdks), which in turn can phosphorylate the retinoblastoma gene product, pRb, to cancel its growth-suppressive function. Hypophosphorylated forms of pRb, present only during the G1 phase, sequester target proteins including known transcription factors, but pRb phosphorylation late in G1 prevents these interactions and thus frees factors to alter the expression of genes required for entry into S phase. Although pRb can act as a regulator of the G1-S transition, its loss is tolerated by most cells, suggesting that its functions overlap with those of other regulators or are restricted to special circumstances under which cells exit the division cycle.