PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites

PARP is a multifunctional protein that can affect genome stability, transcr iption control, telomere length and cell death. Recently we have reported t hat PARP binds to and enhances B-MYB transactivating potential. B-MYB is a potentially oncogenic transcription factor involved in mammalian cell proli feration, survival and differentiation. B-MYB gene expression is growth reg ulated and B-MYB protein is phosphorylated during S phase by cyclin A or E/ cdk2 kinase, resulting in augmented transactivating potential. Here we show that PARP induces phosphorylation of B-MVB protein at cdk2 phosphorylation sites, since a B-MYB protein with mutated cdk2 phosphorylation sites is re fractory to PARP-induced phosphorylation and co-activation in mammalian cel ls. We propose that PARP functions as a B-MYB co-factor by promoting cyclin /cdk2-dependent B-MYB phosphorylation. These results highlight a novel role for PARP as a factor that integrates cyclin-dependent kinases signaling wi th gene transcription.