HSP90 Co-chaperones in saccharomyces cerevisiae

Abstract

Heat-shock response is a general mechanism through which cells cope with external, as well as internal, stresses. Although the heat-shock response is elicited under conditions of stress, proteins involved in this set of pathways are also necessary for basic maintenance of cellular constituents, which involves regulation of proper levels, folded states, and conformations of proteins. Heat shock proteins play key roles in ensuring the fine-tuning and integrity of the signal transduction pathways, including those involved in cellular proliferation and cell cycle regulation. Understanding the function of the heat shock proteins is, therefore, central to our knowledge of proper cell regulation and how it might go awry; it is also essential for developing productive interventions to prevent the loss of this regulation. Hsp90 is an essential, abundant, and highly conserved heat shock protein. It interacts with a large number and variety of wild type and mutant proteins that are partially folded, or adopt unstable or inactive conformations. Because of its ability to buffer the morphologic variability within the cell and allow mutant or partially folded proteins to perform wild-type functions Hsp90 is considered a molecular "evolutionary capacitor" [142]. Hsp90 is also a global signal transduction regulator that can modulate responses of numerous signaling molecules to intra- and extracellular stimuli. A subset of Hsp90 substrate proteins are involved in the regulation of cellular proliferation and transformation. Deeper understanding of the regulation of these substrates by Hsp90 will further our knowledge of tumorigenesis in general, and thus lead to approaches through which it can be prevented. Hsp90 is a molecular chaperone that performs its roles in concert with other proteins, collectively referred to as Hsp90 co-chaperones. Most mammalian Hsp90 co-chaperones are conserved in Saccharomyces cerevisiae (see Table 1). On the one hand, this facilitates (the) analysis of Hsp90 co-chaperones in vivo with a facile and genetically tractable system. On the other hand, the absence of certain mammalian homologs of the Hsp90 complex in yeast affords an opportunity to use yeast as a "bag of enzymes" to study in vivo precisely those components that are missing. © 2007 Springer.