Regulation of NF-kB signalling cascade by immunophilins.

LAGADARI M, DE LEO SA, CAMISAY MF, GALIGNIANA MD, ERLEJMAN AG

CURRENT MOLECULAR PHARMACOLOGY

BENTHAM SCIENCE

Lugar: Bussum; Año: 2015 vol. 9 p. 99 - 108

The fine regulation of signalling cascades is a key event responsible to maintain the appropriate functional properties of a cell when a given stimulus must trigger a specific biological response. In this sense, cumulative experimental evidence during the last years have shown that high molecular weight immunophilins possess a fundamental importance in the regulation of many of those processes, in particular in the steroid receptor field. TPR-domain immunophilins such as FKBP51 and FKBP52 play a cardinal role, usually in an antagonistic fashion, in the regulation of several receptors of this family of ligand dependent transcription factors. These Hsp90-associated cochaperones form a functional unit with the chaperone influencing ligand binding capacity, receptor trafficking and steroid-dependent transcriptional activity. Recently, it was demonstrated that the same immunophilins are able to regulate the NF-kB signalling cascade in an Hsp90 independent manner. In this article we summarize these properties and discuss the relevance of this novel regulatory pathway in the context of the pleiotropic actions managed by NF-kB in several cell types and tissues.