Human FKBP5 Negatively Regulates Transcription through Inhibition of P-TEFb Complex Formation.

ABSTRACT: Although a large number of recent studies indicate strong association of FKBP5 (aka FKBP51) functions with various stress-related psychiatric disorders, the overall mechanisms are poorly understood. Beyond a few studies indicating its functions in regulating glucocorticoid receptor, and AKT signaling pathways, other functional roles (if any) are unclear. Here, we report an antiproliferative role of human FKBP5 through negative regulation of expression of proliferation-related genes. Mechanistically, we show that, owing to the same region of interaction on cyclin-dependent kinse 9 (CDK9), human FKBP5 directly competes with cyclin T1 for functional positive transcription elongation factor b (P-TEFb) complex formation. In vitro biochemical assays, coupled wi

SUBMITTER: Mall DP 

PROVIDER: S-EPMC8773085 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature