Hsp110 protects heat-denatured proteins and confers cellular thermoresistance.
The 110-kDa heat shock protein (hsp110) has long been recognized as one of the primary heat shock proteins in mammalian cells. It belongs to a recently described protein family that is a significantly diverged subgroup of the hsp70 family and has been found in organisms as diverse as yeast and mammals. We describe here the first analysis of the ability of hsp110 to protect cellular and molecular targets from heat damage. It was observed that the overexpression in vivo of hsp110 conferred substantial heat resistance to both Rat-1 and HeLa cells. In vitro heat denaturation and refolding assays demonstrate that hsp110 is highly efficient in selectively recognizing denatured proteins and maintaining them in a soluble, folding-competent state and is significantly more efficient in performing this function than is hsc70. hsp110-bound proteins can then be refolded by the addition of rabbit reticulocyte lysate or hsc70 and Hdj-1, whereas Hdj-1 does not itself function as a co-chaperone in folding with hsp110. hsp110 is one of the principal molecular chaperones of mammalian cells and represents a newly identified component of the primary protection/repair pathway for denatured proteins and thermotolerance expression in vivo.
Oh
H J
HJ
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Chen
X
X
Subjeck
J R
JR
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006224:Cricetinae; D050883:HSC70 Heat-Shock Proteins; D050957:HSP110 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D011489:Protein Denaturation; D017510:Protein Folding; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D050957:HSP110 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C097205:HSPH1 protein, human; D006360:Heat-Shock Proteins; C494655:Hspa4 protein, rat; C494373:Hspa8 protein, rat