Proline isomerases function during heat shock.
The cyclophilins (CYPs) and FK506 binding proteins (FKBPs) are two families of distinct proline isomerases that are targets for a number of clinically important immunosuppressive drugs. Members of both families catalyze cis/trans isomerization of peptidyl-prolyl bonds, which can be a rate-limiting step during protein folding in vitro and in vivo. We demonstrate in Saccharomyces cerevisiae that heat shock causes a 2- to 3-fold increase in the level of mRNA encoded by the major cytoplasmic CYP gene, CYP1. The cloned CYP1 promoter confers heat-inducible expression upon a reporter gene, and transcriptional induction is mediated through sequences similar to the consensus heat shock response element. Disruption of CYP1 decreases survival of cells following exposure to high temperatures, indicating that CYP1 plays a role in the stress response. A second CYP gene, CYP2, encodes a cyclophilin that is located within the secretory pathway. Its expression is also stimulated by heat shock, and cells containing a disrupted CYP2 allele are more sensitive than wild-type cells to heat. By contrast, expression of the FKB1 gene, which encodes a cytoplasmic member of the yeast FKBP family, is neither heat responsive nor necessary for survival after exposure to heat stress.
Sykes
K
K
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9050.
Gething
M J
MJ
Sambrook
J
J
D000483:Alleles; D000591:Amino Acid Isomerases / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003001:Cloning, Molecular; D003524:Cyclosporins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D005838:Genotype; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006358:Hot Temperature; D007700:Kinetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D019696:Peptidylprolyl Isomerase; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D003524:Cyclosporins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus