title: Rapid histone H3 phosphorylation in response to growth factors, phorbol esters, okadaic acid, and protein synthesis inhibitors.
abstract: When quiescent cells are stimulated with growth factors, phorbol esters, okadaic acid, or protein synthesis inhibitors, the early-response genes, which include c-fos and c-jun, are rapidly induced. The earliest growth factor- and phorbol ester-stimulated nuclear signaling events concomitant with proto-oncogene induction are the rapid phosphorylation of two chromatin-associated proteins, pp33 and pp15. We show here that the tumor promoter okadaic acid, which inhibits protein phosphatases 1 and 2A, and the protein synthesis inhibitors anisomycin and cycloheximide also stimulate pp33 and pp15 phosphorylation. Using transcriptional inhibitors, we show that this response is not a consequence of early gene induction. By peptide mapping and microsequencing, chromatin-associated pp15 is identified as histone H3. Upon stimulation, histone H3 is rapidly phosphorylated on serine residues within its highly charged, basic N-terminal domain. Thus, these diverse agents elicit a common early nuclear signal modulating nucleosomal structure or function, potentially contributing to conformational regulation of proto-oncogene induction.
authors.affiliation: Department of Biochemistry, Oxford University, England.
authors.forename: L C
authors.initials: LC
authors.lastname: Mahadevan
authors.forename: A C
authors.initials: AC
authors.lastname: Willis
authors.forename: M J
authors.initials: MJ
authors.lastname: Barratt
mesh_terms: D000546:Amanitins / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000187:drug effects / Q000502:physiology; D019319:Okadaic Acid; D010710:Phosphates / Q000378:metabolism; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000546:Amanitins; D002843:Chromatin; D004988:Ethers, Cyclic; D006133:Growth Substances; D006657:Histones; D009707:Nucleosomes; D010710:Phosphates; D010748:Phosphopeptides; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D019319:Okadaic Acid; D000841:Anisomycin; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate