title: Selective augmentation of histone H1 phosphorylation sites by interaction of poly(ADP-ribose) polymerase and cdc2-kinase: comparison with protein kinase C.
abstract: The molecular interactions between PARP I, cdc2-kinase, PKC and histone H1 were determined with the aid of the common phosphate acceptor function of histone H1 to both kinases. PKC phosphorylates both histone H1 and PARP I and PARP I augments the acceptor function of histone H1. When both acceptors (PARP I and histone H1) are present an apparent distributive phosphorylation of both acceptors takes place. In contrast, cdc2-kinase only phosphorylates histone H1, and the activation of this reaction by PARP I does not involve PARP I-cdc2-kinase binding only PARP I-histone H1 association. Since the phosphorylation of histone H1 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 H1 by cdc2-kinase following PARP I-histone H1 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 histone H1, following PARP I binding. The cell biologic significance of this reaction in PARP I ligand-induced enzyme induction is briefly analysed.
authors.affiliation: Department of Anatomy and Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: P I
authors.initials: PI
authors.lastname: Bauer
authors.forename: K G
authors.initials: KG
authors.lastname: Buki
authors.forename: E
authors.initials: E
authors.lastname: Kun
mesh_terms: D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D006657:Histones / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D006657:Histones; D011065:Poly(ADP-ribose) Polymerases; D011494:Protein Kinases; C102333:histone H1 kinase; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases