of the HSP. Inhibition of HSP90 activity by geldanamycin derivatives is based on their binding to the ATP binding site. Client proteins Client proteins are steroid hormone receptors, kinases, ubiquitin ligases, transcription factors and proteins from many more families. Examples of HSP90AB1 client proteins are p38MAPK/MAPK14 (mitogen activated protein kinase 14), ERK5 (extracellular regulated kinase 5), or the checkpoint kinase Wee1. Clinical significance Cystic fibrosis (CF, mucoviscidosis) is a genetic disease with increased viscosity of various secretions leading to organ failure of lung, pancreas and other organs. It is caused in nearly all cases by a deletion of phenylalanine 508 of CFTR (cystic fibrosis transmembrane conductance regulator). This mutation causes a maturation defect of this ion channel protein with increased degradation, mediated by HSPs. Deletion of the co-chaperone AHA1 (activator of heat shock 90kDa protein ATPase homolog 1) leads to stabilization of CFTR and opens up a perspective for a new therapy. Cancer HSP90AB1 and its co-chaperones are frequently overexpressed in cancer cells. They are able to stabilize mutant proteins thereby allowing survival and increased proliferation of cancer cells. This renders HSPs potential targets for cancer treatment. In salivary gland tumors, expression of HSP90AA1 and HSP90AB1 correlates with malignancy, proliferation and metastasis. The same is basically true for lung cancers where a correlation with survival was found. Notes References Further reading