The steroid receptor-associated TPR cochaperones FKBP51, FKBP52, CyP40 and PP5 have
non-redundant roles in steroid receptor function that impact steroid hormone-binding affinity, nucleocyoplasmic
shuttling and transcriptional activation of target genes in a tissue-specific manner. Aberrant
expression of these TPR immunophilins has the potential to cause steroid-based diseases, including
breast and prostate cancer, diabetes and metabolic disorders, male and female infertility and major
depressive and neurodegenerative disorders. This review summaries the function of these proteins as cochaperones in
steroid receptor-Hsp90 complexes and elaborates on their role in alternative, Hsp90-dependent and -independent signalling
pathways not involving steroid receptors. The review also extensively covers current knowledge of the link between
the steroid receptor-associated immunophilins and human disease. An improved understanding of their mechanisms of action
has revealed opportunities for molecular therapies to enhance or inhibit cellular processes under their control that
contribute both to human health and disease.
Keywords: Steroid receptor-associated TPR immunophilins, Heat shock protein 90 (Hsp90), steroid receptor signalling,
Hsp90-dependent and -independent signalling, TPR cochaperones in health and disease, diabetes and metabolic disorders, neurodegenerative
disease, therapeutic targeting.
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