The retinoblastoma protein: More than meets the eyes

Over the past 10 years, tumor suppressor genes involved in many human malignancies have been isolated. The retinoblastoma gene was the first such tumor suppressor gene to be cloned. Analysis of the retinoblastoma gene and the retinoblastoma gene product (pRb) has increased our understanding of its diverse functions which include the regulation of cell cycle progression, transcription factor activity, cellular differentiation, and embryonic development. Analysis of proteins which interact with pRb has provided insight into the molecular basis for how pRb regulates these diverse processes. Functional deletion of pRb by homologous recombination proved that pRb indeed has an essential role for normal mouse development. Further study of cells and cell lines derived from these pRb-deficient mouse embryos has provided clues to the molecular basis for how pRb functions to suppress tumor formation in specific tissues. Our present hypothesis is that although pRb has universal effects on the regulation of the cell cycle, it has tissue-restricted effects on the regulation of differentiation, development and tumor-predisposition. This review will address recent developments in the understanding of these functions of pRb.