Dissecting functions of the retinoblastoma tumor suppressor and the related pocket proteins by integrating genetic, cell biology, and electrophoretictechniques

The members of the 'pocket protein' family, comprising the retinoblastoma t umor suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell proliferation and modulate fundamental biological processes including embryonic development, differentiation, homeostatic tissue renewal, and de fense against cancer. The large, multidomain pocket proteins act by binding a plethora of cell fate-determining and growth-stimulatory proteins, the m ost prominent of which are the E2F/DP transcription factors. These protein- protein interactions are in turn regulated by carefully orchestrated phosph orylation events on multiple serine and threonine residues of pRB, p107, an d p130, events which are carried out, at least in part, by the cyclin-depen dent kinases that form the key elements of the cell cycle machinery. Here w e discuss the recently obtained new insights into the diverse functions of the pRB family, and show examples of how integration of genetic, cell biolo gy, and a range of electrophoretic approaches help to advance our understan ding of the biological roles played by the pocket proteins in both normal a nd cancer cells.