Control of SV40 DNA Replication by Protein Phosphorylation

Protein phosphorylation is a major regulatory mechanism in eucaryotic cells. Although much is known about the protein kinases involved, and some information about protein phosphatases is available, a detailed understanding of the role of protein phosphorylation in modulating the function of cellular regulatory proteins has been difficult to achieve. Viral regulatory proteins, such as simian virus 40 (SV40) large tumor antigen (T Ag), represent an experimentally advantageous system to study the modulation of protein function by phosphdrylation. T Ag is a complex multifunctional phosphoprotein with sequence-specific DNA binding activity, DNA helicase activity and the ability to associate with a number of cellular proteins (Fig. 1). It is required for the initiation of SV40 DNA replication in infected monkey cells or in a cell-free system in vitro (reviewed recendy by Prives 1990; Borowiec et al. 1990; Fanning 1992a; Fanning and Knippers 1992). Indeed, T Ag is the only viral protein required for viral DNA replication. SV40 DNA replication has therefore been useful in identifying cellular replication proteins and their functions.