Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription

Modulation of the activity of the upstream binding factor (UBF) plays a key role in cell cycle-dependent regulation of rRNA synthesis. Activation of r DNA transcription on serum stimulation requires phosphorylation of UBF at s erine 484 by G(1)-specific cyclin-dependent kinase (cdk)/cyclin complexes. After G(1) progression UBF is phosphorylated at serine 388 by cdk2/cyclin E and cdk2/cyclin A. Conversion of serine 388 to glycine abolishes UBF activ ity, whereas substitution by aspartate enhances the transactivating functio n of UBF. Protein-protein interaction studies reveal that phosphorylation a t serine 388 is required for the interaction between RNA polymerase I and U BF. The results suggest that phosphorylation of UBF represents a powerful m eans of modulating the assembly of the transcription initiation complex in a proliferation- and cell cycle-dependent fashion.