Abstract
The molecular chaperone HSP90, in concert with the co-chaperone CDC37, facilitates the maturation and modulates the activity of a variety of protein kinases. In this article, Gaude and colleagues described the dual activities of the HSP90-CDC37 chaperone machinery in maintaining the stability while inhibiting the activity of LKB1 kinase. LKB1 in complex with HSP90-CDC37 has a longer half-life but is incapable of autophosphorylation, and its kinase activity is increased upon HSP90 inhibition. Dissociation of HSP90 from LKB1 results in its interaction with HSP/HSC70. HSP/HSC70 recruits the ubiquitin ligase CHIP, which ubiquitinates LKB1, leading to its proteasome-mediated degradation. These data emphasize the versatile roles of molecular chaperones associated with LKB1 and warrant future studies to characterize the clinical relevance of these observations.