p107 and p130: versatile proteins with interesting pockets

p107 and p130 were originally identified as targets of the transforming domains of viral oncoproteins encoded by small DNA tumor viruses. Together with pRB, the protein product of the retinoblastoma gene (Rb), p107 and p130 represent a family of closely related proteins that play critical roles in the regulation of cell proliferation. p107, p130, and pRB are transcriptional regulators whose activities are coupled to the cell cycle. Each of these proteins associates with E2F and is directly regulated by phosphorylation by cyclin-dependent kinases. In vivo studies of p107 and p130 function have revealed that their roles overlap extensively with one another and with pRB. In addition, the analysis of mice (and cell lines derived from these animals) deficient in these proteins shows that the individual members of this family harbor distinct functions that, at present, are poorly understood. The characterization of tumor cells continues to emphasize the important and somewhat unique role of pRB in tumor suppression, and the evidence linking the specific inactivation of p107 or p130 to tumor development remains quite limited. In this review we summarize the biochemical and functional properties of p107 and p130, and we compare and contrast these properties to those of pRB.