Selective augmentation of histone H1 phosphorylation sites by interaction of poly(ADP-ribose) polymerase and cdc2-kinase: Comparison with protein kinase C

The molecular interactions between PARP I, cdc2-kinase, PKC and histone HI were determined with the aid of the common phosphate acceptor function of histone H I to both kinases. PKC phosphorylates both histone HI and PARP I and PARP I augments the acceptor function of histone H1. When both acceptors (PARP I and histone HI) are present an apparent distributive phosphorylation of both acceptors takes place. In contrast, cdc2-kinase only phosphorylates. historic Hl, and the activation of this reaction by PARP I does not involve PARP I-cdc2-kinase binding only PARP I-histone H I association. Since the phosphorylation of histone HI by PKC is a model reaction with no apparent physiologic consequences, the PARP I activated phosphorylation of histone H1 by cdc2-kinase, by contrast, reflects a physiologically meaningful regulation of the linker histone by a cyclin dependent kinase (cdc2-kinase). The increased phosphorylation of histone Hi by cdc2-kinase following PARP I-histone HI binding results in the appearance of new phosphorylated histone. H1 polypeptides. as measured by proteolytic digestion and re-electrophoresis of cdc2-kinase phosphorylated polypeptides, indicating a probable conformational change in historic HI, following PARP I binding. The cell biologic significance of this reaction in PARP I li-and-induced enzyme induction is briefly analysed.