Signals regulating p53- and Rb-mediated negative cell growth

IN NORMAL CELLS, negative growth regulators, such as p53 and retinoblastoma (Rb), are responsible for the maintenance of growth control. Loss of p53 and Rb function leads to loss of growth control and often occurs in tumor development. Various signals activate p53, and in turn, p53 functions as a transcription factor to activate genes, such as WAF1/cip1, a potent inhibitor of the cell cycle. The phosphorylation status of Rb regulates its ability to bind other proteins and inhibit cell growth. Transforming growth factor-beta (TGF-β) appears to activate Rb by eliminating the activity of the kinases responsible for phosphorylating and inactivating Rb. The identification of upstream and downstream effectors in both the p53 and Rb pathways will be important to our understanding of tumor development and for devising novel treatment strategies.