Role of the Hsp90-Immunophilin Heterocomplex in Cancer Biology

(E-pub Ahead of Print)

Author(s): Sonia A. De Leo, Nadia R. Zgajnar, Cecilia M. Lotufo, Gisela I. Mazaira, Alejandra G. Erlejman, Mario D. Galigniana*.

Journal Name: Current Cancer Therapy Reviews

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The identification of new factors that may function as cancer markers and become eventual pharmacologic targets is a challenge that may influence the management of the tumor development and management. Recent discoveries connecting Hsp90-binding immunophilins with the regulation of signalling events that can modulate cancer progression transform this family of proteins in potential unconventional factors that may impact on the screening and diagnosis of malignant diseases. Immunophilins are molecular chaperones that groups a family of intracellular receptors for immunosuppressive compounds. A subfamily of the immunophilin family is characterized by showing structural tetratricopeptide repeats, protein domains that are able to interact with the C-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 is 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 processes such as apoptosis, carcinogenesis progression, and chemoresistance. While the expression levels of some members of the immunophilin family are affected in both cancer cell lines and human cancer tissues compared to normal samples, novel regulatory mechanisms have emerged during the last few years for several client-factors of immunophilins that are major players in cancer development and progression, among them steroid receptors, the transctiption factor NF-κB and the catalytic subunit of telomerase, hTERT. In this review, recent findings related to the biological properties of both iconic Hsp90-binding immunophilins, FKBP51 and FKBP52, are reviewed within the context of their interactions with those chaperoned client-factors. The potential roles of both immunophilins as potential cancer biomarkers and non-conventional pharmacologic targets for cancer treatment are discussed.

Keywords: Heat-shock proteins immunophilins; cancer; peptidylprolyl isomerase; TPR protein; steroid receptor; NF-κB

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(E-pub Ahead of Print)
DOI: 10.2174/1573394715666190102120801
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