Our laboratory studies the role of the retinoblastoma protein (pRB) pathway in differentiation and cancer. The retinoblastoma protein acts to control proliferation at least in part by regulating transcription of genes required for DNA synthesis. Recent work demonstrates that pRB can also promote the synthesis of gene products involved in generating the differentiated phenotype of a number of different tissue types. Further, pRB plays a role in enforcing the permanent cell cycle withdrawal associated with terminal differentiation and the tumor-suppressive process of senescence.