FKBP51 and FKBP52 are diverse regulators of steroid hormone receptor signaling, including receptor maturation, hormone binding and nuclear translocation. Although structurally similar, they are functionally divergent, which is largely attributed to differences in the FK1 domain and the proline-rich loop. FKBP51 and FKBP52 have emerged as likely contributors to a variety of hormone-dependent diseases, including stress-related diseases, immune function, reproductive functions and a variety of cancers. In addition, recent studies have implicated FKBP51 and FKBP52 in Alzheimer's disease and other protein aggregation disorders. This review summarizes our current understanding of FKBP51 and FKBP52 interactions within the receptor-chaperone complex, their contributions to health and disease, and their potential as therapeutic targets for the treatment of these diseases.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229651 | PMC |
http://dx.doi.org/10.1016/j.tem.2011.08.001 | DOI Listing |
Adv Sci (Weinh)
November 2024
Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
In the realm of neural regeneration post-spinal cord injury, hydrogel scaffolds carrying induced neural stem cells (iNSCs) have demonstrated significant potential. However, challenges such as graft rejection and dysfunction caused by mitochondrial damage persist after transplantation, presenting formidable barriers. Tacrolimus, known for its dual role as an immunosuppressant and promoter of neural regeneration, holds the potential for enhancing iNSC transplantation.
View Article and Find Full Text PDFChemMedChem
September 2024
Department of Chemistry and Biochemistry Clemens-Schöpf-Institute, Technical University Darmstadt, Alarich-Weiss Straße 4, 64287, Darmstadt, Germany.
The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51-selective ligands such as SAFit2 are too large and lack drug-like properties.
View Article and Find Full Text PDFEur J Med Chem
April 2024
Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, 17164, Solna, Sweden.
The heat shock protein 90 kDa (Hsp90) molecular chaperone machinery is responsible for the folding and activation of hundreds of important clients such as kinases, steroid hormone receptors, transcription factors, etc. This process is dynamically regulated in an ATP-dependent manner by Hsp90 co-chaperones including a group of tetratricopeptide (TPR) motif proteins that bind to the C-terminus of Hsp90. Among these TPR containing co-chaperones, FK506-binding protein 51 kDa (FKBP51) is reported to play an important role in stress-related pathologies, psychiatric disorders, Alzheimer's disease, and cancer, making FKBP51-Hsp90 interaction a potential therapeutic target.
View Article and Find Full Text PDFNat Struct Mol Biol
December 2023
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding, aided by co-chaperones. In vivo, the co-chaperones FKBP51 and FKBP52 antagonistically regulate GR activity, but a molecular understanding is lacking.
View Article and Find Full Text PDFNat Struct Mol Biol
December 2023
Department of Chemistry, Technical University Darmstadt, Darmstadt, Germany.
The Hsp90 co-chaperones FKBP51 and FKBP52 play key roles in steroid-hormone-receptor regulation, stress-related disorders, and sexual embryonic development. As a prominent target, glucocorticoid receptor (GR) signaling is repressed by FKBP51 and potentiated by FKBP52, but the underlying molecular mechanisms remain poorly understood. Here we present the architecture and functional annotation of FKBP51-, FKBP52-, and p23-containing Hsp90-apo-GR pre-activation complexes, trapped by systematic incorporation of photoreactive amino acids inside human cells.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!