RRC ID 1598
Author Okada M, Hatakeyama T, Itoh H, Tokuta N, Tokumitsu H, Kobayashi R.
Title S100A1 is a novel molecular chaperone and a member of the Hsp70/Hsp90 multichaperone complex.
Journal J Biol Chem
Abstract Although calmodulin is known to be a component of the Hsp70/Hsp90 multichaperone complex, the functional role of the protein remains uncertain. In this study, we have identified S100A1, but not calmodulin or other S100 proteins, as a potent molecular chaperone and a new member of the multichaperone complex. Glutathione S-transferase pull-down assays and co-immunoprecipitation experiments indicated the formation of stable complexes between S100A1 and Hsp90, Hsp70, FKBP52, and CyP40 both in vitro and in mammalian cells. S100A1 potently protected citrate synthase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, and rhodanese from heat-induced aggregation and suppressed the aggregation of chemically denatured rhodanese and citrate synthase during the refolding pathway. In addition, S100A1 suppressed the heat-induced inactivation of citrate synthase activity, similar to that for Hsp90 and p23. The chaperone activity of S100A1 was antagonized by calmodulin antagonists, such as fluphenazine and prenylamine, that is, indeed an intrinsic function of the protein. The overexpression of S100A1 in COS-7 cells protected transiently expressed firefly luciferase and Escherichia coli beta-galactosidase from inactivation during heat shock. The results demonstrate a novel physiological function for S100A1 and bring us closer to a comprehensive understanding of the molecular mechanisms of the Hsp70/Hsp90 multichaperone complex.
Volume 279(6)
Pages 4221-33
Published 2004-2-6
DOI 10.1074/jbc.M309014200
PII M309014200
PMID 14638689
MeSH Amino Acid Sequence Animals Brain / metabolism Calcium / metabolism Calcium-Binding Proteins / chemistry Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism* Calmodulin / metabolism Carrier Proteins / chemistry Carrier Proteins / genetics Carrier Proteins / metabolism Cattle Cyclophilins* HSP70 Heat-Shock Proteins / chemistry HSP70 Heat-Shock Proteins / genetics HSP70 Heat-Shock Proteins / metabolism* HSP90 Heat-Shock Proteins / chemistry HSP90 Heat-Shock Proteins / genetics HSP90 Heat-Shock Proteins / metabolism* Humans In Vitro Techniques Kinetics Macromolecular Substances Molecular Chaperones / chemistry Molecular Chaperones / genetics Molecular Chaperones / metabolism* Molecular Sequence Data Peptidylprolyl Isomerase / chemistry Peptidylprolyl Isomerase / genetics Peptidylprolyl Isomerase / metabolism Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism S100 Proteins Surface Plasmon Resonance Tacrolimus Binding Proteins / chemistry Tacrolimus Binding Proteins / genetics Tacrolimus Binding Proteins / metabolism
IF 4.106
Times Cited 36
DNA material pHSP90 (RDB01127)