Role of the Hsp90-immunophilin heterocomplex in cancer disease

DE LEO SA, ZGAJNAR NR, MAZAIRA GI, ERLEJMAN AG, GALIGNIANA MD

CURRENT CANCER THERAPY REVIEWS

Bentham Publishers

Año: 2020 vol. 16 p. 19 - 28

1573-3947

The identification of new factors that may function as cancer markers and becomeeventual pharmacologic targets is a challenge that may influence the management of tumor developmentand management. Recent discoveries connecting Hsp90-binding immunophilins with theregulation of signalling events that can modulate cancer progression transform this family of proteinsin potential unconventional factors that may impact on the screening and diagnosis of malignantdiseases. Immunophilins are molecular chaperones that group a family of intracellular receptorsfor immunosuppressive compounds. A subfamily of the immunophilin family is characterizedby showing structural tetratricopeptide repeats, protein domains that are able to interact with theC-terminal end of the molecular chaperone Hsp90, and via the proper Hsp90-immunophilin complex,the biological properties of a number of client-proteins involved in cancer biology are modulated.Recent discoveries have demonstrated that two of the most studied members of this Hsp90-binding subfamily of immunophilins, FKBP51 and FKBP52, participate in several cellular processessuch as apoptosis, carcinogenesis progression, and chemoresistance. While the expressionlevels of some members of the immunophilin family are affected in both cancer cell lines andhuman cancer tissues compared to normal samples, novel regulatory mechanisms have emergedduring the last few years for several client-factors of immunophilins that are major players in cancerdevelopment and progression, among them steroid receptors, the transctiption factor NF-κBand the catalytic subunit of telomerase, hTERT. In this review, recent findings related to the biologicalproperties of both iconic Hsp90-binding immunophilins, FKBP51 and FKBP52, are reviewedwithin the context of their interactions with those chaperoned client-factors. The potentialroles of both immunophilins as potential cancer biomarkers and non-conventional pharmacologictargets for cancer treatment are discussed.Keywords: Heat-shock proteins; immunophilins; cancer; peptidylprolyl isomerase;