Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52

Interferon regulatory factor-4 (IRF-4) plays an important role in immunoreg ulatory gene expression in B and T lymphocytes and is also highly expressed in human T cell leukemia virus type 1 infected cells. In this study, we ch aracterize a novel interaction between IRF-4 and the FK506-binding protein 52 (FKBP52), a 59 kDa member of the immunophilin family with peptidyl-proly l isomerase activity (PPlase). IRF-4-FKBP52 association inhibited IRF4-PU.1 binding to the immunoglobulin light chain enhancer Elambda 2-4 as well as IRF-4-PU. 1 transactivation, effects that were dependent on functional PPla se activity. FKBP52 association also resulted in a structural modification of IRF-4, detectable by immunoblot analysis and by IRF-4 partial proteolysi s. These results demonstrate a novel posttranslational mechanism of transcr iptional control, mediated through the interaction of an immunophilin with a transcriptional regulator.