Biological relevance of Hsp90-binding immunophilins in cancer

GISELA I. MAZAIRA; MARÍA FERNANDA CAMISAY; SONIA DE LEO; ALEJANDRA G. ERLEJMAN; MARIO D. GALIGNIANA

INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER.

JOHN WILEY & SONS INC

Lugar: New York; Año: 2016 vol. 138 p. 797 - 808

0020-7136

Immunophilins are a family of intracellular receptors for immunosuppressive drugs. Those immunophilins that are related toimmunosuppression are the smallest proteins of the family, i.e., FKBP12 and CyPA, whereas the other members of the familyhave higher molecular weight because the show additional domains to the drug-binding site. Among these extra domains, theTPR-domain is perhaps the most relevant because it permits the interaction of high molecular weight immunophilins with the90-kDa heat-shock protein, Hsp90. This essential molecular chaperone regulates the biological function of several proteinkinases, oncogenes, protein phosphatases, transcription factors and cofactors . Hsp90-binding immunophilins where first characterized due to their association with steroid receptors. They regulate the cytoplasmic transport and the subcellular localization of these and other Hsp90 client proteins, as well as transcriptional activity, cell proliferation, cell differentiation and apoptosis. Hsp90-binding immunophilins are frequently overexpressed in several types of cancers and play a key role in cell survival. In this article we analyze the most important biological actions of the best characterized Hsp90-binding immunophilins in both steroid receptor function and cancer development and discuss the potential use of these immunophilins for therapeutic purposes as potential targets of specific small molecules.