Differential Dynamics and Roles of FKBP51 Isoforms and Their Implications for Targeted Therapies

Abstract

Abstract The expression of FKBP5, and its resulting protein FKBP51, is strongly induced by stress and glucocorticoids. Numerous studies have explored their involvement in a plethora of cellular processes and diseases, including psychiatric disorders, inflammatory conditions and cancer. However, there is a lack of knowledge on the role of the different RNA splicing variants and the two protein isoforms that originate from the human FKBP5 locus, especially in response to glucocorticoids. In this study we use in vitro models as well as peripheral blood cells of a human cohort to show that the two expressed variants are both dynamically upregulated following dexamethasone. We also investigate the subcellular localization of the protein isoforms, their degradation dynamics as well as their differential role in known cellular pathways. The results shed light on the difference of the two variants and highlight the importance of differential analyses in future studies with implications for targeted drug design.