Stress activation of heat shock factor (HSF1) involves the conversion of repressed monomers to DNA-binding homotrimers with increased transcriptional capacity and results in transcriptional up-regulation of the heat shock protein (hsp) gene family. Cells tightly control the activity of HSF1 through interactions with hsp90 chaperone complexes and through integration into a number of different si...

Folding of newly synthesized cytosolic proteins has been proposed to require assistance by Hsp70 chaperones. We investigated whether two Hsp70 homologs of Escherichia coli, DnaK and HscA, have this role in vivo. Double mutants lacking dnaK and hscA were viable and lacked defects in protein folding at intermediate temperature. After heat shock, a subpopulation of pre-existing proteins slowly agg...

Hsp33, a member of a newly discovered heat shock protein family, was found to be a very potent molecular chaperone. Hsp33 is distinguished from all other known molecular chaperones by its mode of functional regulation. Its activity is redox regulated. Hsp33 is a cytoplasmically localized protein with highly reactive cysteines that respond quickly to changes in the redox environment. Oxidizing c...

Heat shock genes encode proteins (hsp's) that play important structural roles under normal circumstances and are essential to the cells' ability to survive environmental insults. Evidence is presented herein that transcriptional regulation of hsp gene expression is linked with the regulation of overall protein synthesis as well as with the accumulation of proteins denatured by stressful events....

The 70 kD heat shock cognate proteins (HSC70s) are constitutive members of the 70 kD heat shock related protein family. We have sequenced the cDNA of a bovine HSC70: clones were isolated from a bovine brain cDNA library in XgtlO (1) by hybridization with probes derived from a rat HSC70 cDNA clone (2); one full-length clone was sequenced. The deduced amino acid sequence matches CNBr-generated pe...

Despite a wealth of information about the structure and composition of steroid receptors and their functional domains, little is known about the role of accessory proteins as mediators of receptor activity. To better define the role of such proteins in estrogen receptor (ER) function, we have used immunoaffinity, steroid affinity, and site-specific DNA-affinity chromatography to identify and ch...

Glucocorticoids are the most important mediator of muscle cachexia in various catabolic conditions. Recent studies suggest that the transcription factor NF-kappaB acts as a suppressor of genes in the ubiquitin-proteasome proteolytic pathway and that glucocorticoids increase muscle proteolysis by downregulating NF-kappaB activity. The heat shock (stress) response, characterized by the induction ...

Tom70 is a mitochondrial protein import receptor composed of 11 tetratricopeptide repeats (TPRs). The first three TPRs form an N-terminal domain that recruits heat shock protein family chaperones, while the eight C-terminal TPRs form a domain that receives, from the bound chaperone, mitochondrial precursor proteins destined for import. Analytical ultracentrifugation and solution small-angle X-r...

Members of the stress protein family such as HSP70 are induced in ischemic tissues and may contribute to the ability of cells to survive episodes of transient circulatory insufficiency. However, the biochemical events that lead to this induction, and their degree of similarity with pathways triggered by heat stress, have not been defined. In this study, we demonstrate that transient exposure of...