title: Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle.
abstract: The Hsc70-interacting protein Hip, a tetratricopeptide repeat protein, participates in the regulation of the eukaryotic 70 kDa heat shock cognate Hsc70. One Hip oligomer binds the ATPase domains of at least two Hsc70 molecules dependent on activation of the Hsc70 ATPase by Hsp40. While hydrolysis remains the rate-limiting step in the ATPase cycle, Hip stabilizes the ADP state of Hsc70 that has a high affinity for substrate protein. Through its own chaperone activity, Hip may contribute to the interaction of Hsc70 with various target proteins. We propose a mechanism for the regulation of eukaryotic Hsc70 that is distinct from that of bacterial Hsp70. The Hsc70/Hsp40/Hip system is apparently independent of a GrpE-like nucleotide exchange factor.
authors.affiliation: Howard Hughes Medical Institute, New York, New York 10021, USA.
authors.forename: J
authors.initials: J
authors.lastname: Höhfeld
authors.forename: Y
authors.initials: Y
authors.lastname: Minami
authors.forename: F U
authors.initials: FU
authors.lastname: Hartl
mesh_terms: D000209:Acute-Phase Proteins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000502:physiology*; D002417:Cattle; D004268:DNA-Binding Proteins / Q000502:physiology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D037102:Lectins / Q000502:physiology*; D037181:Lectins, C-Type; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides / Q000235:genetics; D014176:Protein Biosynthesis / Q000502:physiology; D017510:Protein Folding
chemical_list: D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C105426:Hip chaperone; D037102:Lectins; D037181:Lectins, C-Type; D018832:Molecular Chaperones; D009711:Nucleotides; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides