The role of E2F transcription factors and the RB gene family in cell biology

The retinoblastoma family genes, RB, RB2/p130 and p107, play a key role in several aspects of cell biology. Specifically, they regulate the cell cycle by the differential binding of retinoblastoma family proteins to the members of the E2F family, which in turn regulate the transcription of several genes involved in DNA synthesis and cell cycle progression. Proteins of the retinoblastoma family are the substrate of different cyclins/cyclin dependent kinases (CDKs) and undergo cyclic phosphorylation and dephosphorylation. Hypophosphorylated retinoblastoma proteins are functionally active and bind E2F family members, thereby inhibiting their function. On the other hand, retinoblastoma proteins are inactive when hyperphosphorylated. Although some data indicate that pRb, pRb2/p130 and p107 are able to compensate each other, their specific binding properties suggest that each member of the family could play a specific role in cell biology. In this review we analyze the role of the RB family and E2F factors in cell biology. Differentiation is accompanied by exit from the cell cycle, dephosphorylation of RB family members and formation of pRB member-E2F complexes. As differentiation proceeds, there is an increase in pRb-E2F and pRB2/p130-E2F complexes. These changes are observed by a quantitative shift of pRb-E2F complexes to pRb2-E2F complexes. These changes modify the levels of free E2F protein and this in turn will affect cell division and cell maturation. In fact, it has been suggested that while E2F1, E2F2 and E2F3 act mainly as inducers of cell cycle progression, E2F4 and E2F5 are important during the differentiation process. These aspects of E2F biology will be discussed as well.