Showing papers by "Mario D. Galigniana published in 2014"
TL;DR: Observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-σκB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity.
78 citations
TL;DR: The mission to rationally develop novel effective small molecules against Hsp90, predicted the potency of the designed compounds by Sybyl surflex Geom X docking method and revealed that Schiff bases derived from 2, 4-dihydroxy benzaldehyde/5-chloro-2,4-dhydroxy Benzaldehyde demonstrated effective binding with the protein.
22 citations
TL;DR: FKBP51 and FKBP52 were first characterized due to their ability to interact with steroid hormone receptors and their potential as pharmacologic targets are reviewed.
Abstract: Immunophilins comprise a family of intracellular proteins with peptidyl-prolyl-(cis/trans)-isomerase activity. These foldases are abundant, ubiquitous, and able to bind immunosuppressant drugs, from which the term immunophilin derives. Family members are found in abundance in virtually all organisms and subcellular compartments, and their amino acid sequences are conserved phylogenetically. Immunophilins possess the ability to function as molecular chaperones favoring the proper folding and biological regulation of their biological actions. Their ability to interact via their TPR domains with the 90-kDa heat-shock protein, and through this chaperone, with several signalling cascade factors is of particular importance. Among the family members, the highly homologous proteins FKBP51 and FKBP52 were first characterized due to their ability to interact with steroid hormone receptors. Since then, much progress has been made in understanding the mechanisms by which they regulate receptor signaling and the resulting roles they play not only in endocrine processes, but also in cell architecture, neurodifferentiation, and tumor progression. In this article we review the most relevant features of these two immunophilins and their potential as pharmacologic targets.
20 citations
TL;DR: A group of Hsp90-binding cochaperones belonging to the immunophilin family plays a cardinal role not only in the mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity.
Abstract: In the absence of ligand, some members of nuclear receptor family such as corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus upon ligand-binding. Other members of the family such as the estrogen receptor are mostly nuclear. Regardless of their primary location, these oligomeric proteins undergo a dynamic nuclear-cytoplasmic shuttling, and their transport through the cytoplasmic compartment has always been assumed to occur in a stochastic manner by simple diffusion. Although heuristic, this oversimplified model has never been demonstrated. Moreover, it has always been assumed that the first step related to receptor activation is the dissociation of the Hsp90-based heterocomplex, a process referred to as `transformation.' Nonetheless, recent experimental evidence indicates that the chaperone machinery is required for the retrotransport of the receptor throughout the cytoplasm and facilitates its active passage through the nuclear pore. Therefore, transformation is actually a nuclear event. A group of Hsp90-binding cochaperones belonging to the immunophilin family plays a cardinal role not only in the mechanism for receptor movement, but also in nuclear events leading to interactions with nuclear sites of action and the regulation of transcriptional activity. In this article we analyze the importance of molecular chaperones and TPR-domain immunophilins in the molecular mechanism of action of steroid receptors.
9 citations
TL;DR: School of Medicine, University of Concepcion, Chile, andDepartamento de Neurodesarrollo y Fisiologia, Division of Neurociencias, Instituto de Fisiology Celular, Universidad Nacional Autonoma of Mexico, Mexico.
Abstract: Fil: Napimoga, Marcelo Henrique. Sao Leopoldo Mandic Institute and Research Center. Laboratory of Immunology and Molecular Biology; Brasil
3 citations