The emerging role of immunophilins in cancer development and progression

GALIGNIANA MD

Paris

Conferencia; Conferencia en el Institut de Cancérologie Gustave Roussy; 2020

Institut de Cancérologie Gustave Roussy- Invitación: Dr Jack-Michel Renoir

Immunophilins are a family of intracellular receptors for immunosuppressive drugs. Those immunophilins that are related to immunosuppression are only the smallest proteins of the family, i.e. FKBP12 and CyPA, whereas the other members of the family have higher molecular weight because the show additional domains to the drug-binding site. Among these extra domains, the TPR-domain is perhaps the most relevant because it permits the interaction of high molecular weight immunophilins with the 90-kDa heat-shock protein, Hsp90. This essential molecular chaperone regulates the biological function of several protein-kinases, 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 seminar I will analyse the most important biological actions of the best characterized Hsp90-binding immunophilins in both steroid receptor function and cancer development, and will also discuss the potential use of these immunophilins with therapeutic purposes as potential targets for specific small molecules.