The retinoblastoma protein: a master regulator of cell cycle, differentiation and apoptosis

The retinoblastoma susceptibility gene is a tumour suppressor and its product retinoblastoma protein (pRb) has been known for 10 years as a repressor of progression towards S phase. Its major activity was supposed to be sequestration or inactivation of the transcription factor E2F which is required for activation of S phase genes. However, within recent years growing evidence has been accumulating for a more general function of pRb at both the transcriptional level and the cellular level. pRb not only regulates the activity of certain protein-encoding genes but also the activity of RNA polymerase pol I and pol III transcription. This protein appears to be the major player in a regulatory circuit in the late G1 phase, the so-called restriction point. Moreover, it is involved in regulating an elusive switch point between cell cycle, differentiation and apoptosis. Here, it seems to cooperate with another major tumour suppressor, p53. Thus, pRb sits at the interface of the most important cell-regulatory processes and therefore deserves close attention by specialists from different fields of research. This review provides an introduction to the complex functions of pRb.