Hsp90 Chaperones

Abstract

Abstract Heat shock protein 90 (Hsp90) is an abundant molecular chaperone especially important in the cytosol of eukaryotic cells. Its function is coupled to large conformational rearrangements within the dimer coupled to nucleotide binding. Hsp90 assists a large set of so‐called ‘client’ proteins to stay folded or to achieve an active conformation. These client proteins include among others protein kinases and many transcription factors such as steroid hormone receptors. The function of the Hsp90 chaperone machinery itself is highly regulated on several levels. A large set of cochaperones as well as post‐translational modifications help to fine‐tune the conformational cycle. Inhibition of the low intrinsic adenosine triphosphatase (ATPase) activity of Hsp90 leads to destabilisation of its clients resulting in their degradation. As many of the clients are oncogenes, inhibition of Hsp90 is an important target in cancer therapy. Key Concepts: Hsp90 is an essential molecular chaperone in eukaryotes. Hsp90 function is coupled to nucleotide‐induced conformational changes. Hsp90 stabilises the active state of a large set of clients. Hsp90 function can be regulated via cochaperones or post‐translational modifications. Inhibition of Hsp90 is an anticancer strategy.