Abstract
The co-chaperone p50/Cdc37 is an important partner for Hsp90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. The Hsp90/Cdc37complex controls the folding of a large proportion of protein kinases and thus stands at the hub of a multitude of intracellular signaling networks. Its effects thus reach beyond the housekeeping pathways of protein folding into regulation of a wide range of cellular processes. Due to its influence in cell growth pathways Cdc37 has attracted much attention as a potential intermediate in carcinogenesis. Cdc37 is an attractive potential target in cancer due to: (1) it may be expressed to high level in some types of cancer and (2) Cdc37 controls multiple signaling pathways. This indicates a potential for: (1) selectivity due to its elevated expression and (2) robustness as the co-chaperone may control multiple growth signaling pathways and thus be less prone to evolution of resistance than other oncoproteins. Cdc37 may also be involved in other aspects of pathophysiology. Protein aggregation disorders have been linked to molecular chaperones and to age related declines in molecular chaperones and co-chaperones. Cdc37 appears to be a potential agent in longevity due to its links to protein folding and autophagy and it will be informative to study the role of Cdc37 maintenance/decline in aging organisms.