The Hsp90-based heterocomplex as essential regulator for cancer disease

GALIGNIANA MD

Heat-shock proteins in signaling pathways

Springer Nature Publishers

Lugar: Zurich; Año: 2019;

Heat-shock protein 90 (HSP90) is a molecular chaperone that represents the most abundant soluble protein of the cell. This chaperone shows intrinsic ATPase activity and associates to a great number of client factors such as steroid receptors, tyrosine-kinases, transcription factors, enzymes, cytoskeletal proteins, channels, histones, etc. Because of these interactions, HSP90 is implicated in diverse biological processes that require critical and coordinated regulatory mechanisms to modulate its activity. HSP90 forms heterocomplexes with other chaperones and co-chaperones such as TPR-domain immunophilins that modulate HSP90 properties and are themselves subject of regulation. In malignancy, HSP90 is essential to preserve the metastable forms of oncoproteins that are usually mutated, overamplified, and sometimes translocated from their normal subcellular compartments. Thus, HSP90 helps to buffer the proteostasis of the cell that is assaulted by the onset of the stress generated by the malignant condition. Consequently, HSP90 is an attractive pharmacologic target, and the pharmaceutical industry has generated over the last years several advances in both the basic biology and the translational drug development around HSP90. This chapter is focused on the multiple aspects by which the HSP90 activity and that related to HSP90-binding proteins, particularly immunophilins, are regulated in malignancy.