CK2: The kinase controlling the Hsp90 chaperone machinery

CK2 is a ubiquitous and essential protein kinase with pleiotropic substrates and function, but it remains unclear how, when, and where CK2 activity is regulated in cells. Hsp90 is a major molecular chaperone that is required for the folding and function of its client proteins. A complex containing Hsp90 and its client protein includes co-chaperones such as steroid hormone receptor-specific FKBP52 and signaling kinase-specific Cdc37. Co-chaperones work cooperatively with Hsp90 to stabilize client proteins and to keep them in a conformation amenable to activation under appropriate conditions. In this review, critical roles of CK2 in the regulation of the Hsp90-mediated chaperone system are described. CK2 phosphorylates and modulates Hsp90 and its co-chaperones FKBP52 and Cdc37. CK2-dependent phosphorylation of Cdc37 is essential for the chaperoning function of Hsp90-Cdc37 for multiple signaling protein kinases. The tumor kinome appears to become addicted to the Hsp90-Cdc37 chaperone system, thus, targeting Hsp90, Cdc37, and CK2 is a promising strategy for cancer treatment. (Part of a Multi-author Review)