Hsp70 molecular chaperones play a variety of functions in every organism,
cell type and organelle, and their activities have been implicated in a number of human
pathologies, ranging from cancer to neurodegenerative diseases. The functions,
regulations and structure of Hsp70s were intensively studied for about three decades,
yet much still remains to be learned about these essential folding enzymes. Genome
sequencing efforts revealed that most genomes contain multiple members of the Hsp70
family, some of which co-exist in the same cellular compartment. For example, the
human cytosol and nucleus contain six highly homologous Hsp70 proteins while the
yeast Saccharomyces cerevisiae contains four canonical Hsp70s and three fungalspecific
ribosome-associated and specialized Hsp70s. The reasons and significance of
the requirement for multiple Hsp70s is still a subject of debate. It has been postulated
for a long time that these Hsp70 isoforms are functionally redundant and differ only by
their spatio-temporal expression patterns. However, several studies in yeast and higher
eukaryotic organisms challenged this widely accepted idea by demonstrating functional
specificity among Hsp70 isoforms. Another element of complexity is brought about by
specific cofactors, such as Hsp40s or nucleotide exchange factors that modulate the
activity of Hsp70s and their binding to client proteins. Hence, a dynamic network of
chaperone/co-chaperone interactions has evolved in each organism to efficiently take
advantage of the multiple cellular roles Hsp70s can play. We summarize here our
current knowledge of the functions and regulations of these molecular chaperones, and
shed light on the known functional specificities among isoforms.
Keywords: Hsp70, Ssa1, chaperone network, functional specificity.
