title: Hsp27 enhances recovery of splicing as well as rephosphorylation of SRp38 after heat shock.
abstract: A heat stress causes a rapid inhibition of splicing. Exogenous expression of Hsp27 did not prevent that inhibition but enhanced the recovery of splicing afterward. Another small heat shock protein, alphaB-crystallin, had no effect. Hsp27, but not alphaB-crystallin, also hastened rephosphorylation of SRp38-dephosphorylated a potent inhibitor of splicing-after a heat shock, although it did not prevent dephosphorylation by a heat shock. The effect of Hsp27 on rephosphorylation of SRp38 required phosphorylatable Hsp27. A Hsp90 client protein was required for the effect of Hsp27 on recovery of spicing and on rephosphorylation of SRp38. Raising the Hsp70 level by either a pre-heat shock or by exogenous expression had no effect on either dephosphorylation of SRp38 during heat shock or rephosphorylation after heat shock. The phosphatase inhibitor calyculin A prevented dephosphorylation of SRp38 during a heat shock and caused complete rephosphorylation of SRp38 after a heat shock, indicating that cells recovering from a heat shock are not deficient in kinase activity. Together our data show that the activity of Hsp27 in restoring splicing is not due to a general thermoprotective effect of Hsp27, but that Hsp27 is an active participant in the (de)phosphorylation cascade controlling the activity of the splicing regulator SRp38.
authors.affiliation: Department of Biochemistry, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Marin-Vinader
authors.forename: Chanseok
authors.initials: C
authors.lastname: Shin
authors.forename: Carla
authors.initials: C
authors.lastname: Onnekink
authors.forename: James L
authors.initials: JL
authors.lastname: Manley
authors.forename: Nicolette H
authors.initials: NH
authors.lastname: Lubsen
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008387:Marine Toxins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D038203:alpha-Crystallin B Chain / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008387:Marine Toxins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D010080:Oxazoles; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C115188:SRSF10 protein, human; D038203:alpha-Crystallin B Chain; D000068103:Serine-Arginine Splicing Factors; C059041:calyculin A