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Proline isomerases function during heat shock

K Sykes1, M J Gething, J Sambrook

  • 1Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas 75235-9050.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 1993
PubMed
Summary
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Heat shock increases levels of cyclophilin (CYP) mRNA in yeast, with CYP1 and CYP2 playing roles in cellular survival during heat stress. FKBP gene expression was unaffected by heat.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cyclophilins (CYPs) and FK506 binding proteins (FKBPs) are proline isomerases crucial for protein folding.
  • These enzymes are targets for immunosuppressive drugs.
  • Peptidyl-prolyl bond isomerization can limit protein folding rates.

Purpose of the Study:

  • To investigate the role of cyclophilins and FKBP in the heat shock response of Saccharomyces cerevisiae.
  • To determine if CYP and FKBP gene expression is affected by heat stress.
  • To assess the necessity of these genes for cellular survival under thermal stress.

Main Methods:

  • Quantitative analysis of mRNA levels in response to heat shock.
  • Reporter gene assays to study promoter activity.

Related Experiment Videos

  • Gene disruption (knockout) studies to assess functional roles in stress survival.
  • Main Results:

    • Heat shock induced a 2- to 3-fold increase in CYP1 mRNA levels.
    • CYP1 promoter contains heat shock response elements, conferring heat-inducible expression.
    • Disruption of CYP1 and CYP2 genes reduced yeast survival after heat exposure.
    • Expression of the FKBP gene (FKB1) was not heat-responsive and not essential for heat survival.

    Conclusions:

    • CYP1 and CYP2 are involved in the yeast heat stress response.
    • Heat shock upregulates the expression of specific cyclophilin genes.
    • Proline isomerases like cyclophilins play a significant role in cellular adaptation to thermal stress.