2 Cytosolic hsp70s of Saccharomyces cerevisiae: Roles in Protein Synthesis, Protein Translocation, Proteolysis, and Regulation

Abstract

I. INTRODUCTION
The 70-kD heat shock proteins, or hsp70s, are highly conserved in all organisms studied so far, from bacteria to yeast to humans. Eukaryotes, including the budding yeast Saccharomyces cerevisiae, encode multiple hsp70s in their genomes. These related proteins are localized to a variety of cellular compartments, including the cytosol, mitochondria, and endoplasmic reticulum (ER). Functionally, the organellar hsp70s are better understood, having major roles in protein translocation and folding. The functions of the cytosolic hsp70s have been more difficult to define, perhaps because these proteins are involved in multiple processes, including translation, protein translocation, protein folding, and regulation of the heat shock response. This chapter reviews evolutionary analyses and genetic data concerning the roles of these proteins in the cytosol.

II. EVOLUTION OF THE HSP70 MULTIGENE FAMILY
To gain a better understanding of the evolutionary relationships among hsp70s across the biological spectrum, a comparison of 36 hsp70s from 25 diverse genera was conducted (Boorstein et al. 1994). The analysis, carried out by both distance-matrix and character-state methods, showed that the eukaryotic hsp70s comprise four distinct clusters (see Fig. 1). These clusters correspond to the intracellular localization of the proteins: the cytosol, the ER, mitochondria, and chloroplasts.

Analysis of the comparisons revealed that eukaryotic hsp70s appear to have evolved from ancestral genes by two types of mechanisms. Mitochondrial and chloroplast hsp70s appear to be derived from the establishment of an endosymbiotic relationship between a eukaryotic host and bacterial cells. Mitochondrial hsp70s are encoded in the nuclei, but they share...