Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52.

Interferon regulatory factor-4 (IRF-4) plays an important role in immunoregulatory 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 characterize a novel interaction between IRF-4 and the FK506-binding protein 52 (FKBP52), a 59 ...
kDa member of the immunophilin family with peptidyl-prolyl isomerase activity (PPIase). IRF-4-FKBP52 association inhibited IRF4-PU.1 binding to the immunoglobulin light chain enhancer E(lambda2-4) as well as IRF-4-PU.1 transactivation, effects that were dependent on functional PPIase activity. FKBP52 association also resulted in a structural modification of IRF-4, detectable by immunoblot analysis and by IRF-4 partial proteolysis. These results demonstrate a novel posttranslational mechanism of transcriptional control, mediated through the interaction of an immunophilin with a transcriptional regulator.
Mesh Terms:
Amino Acid Sequence, Animals, B-Lymphocytes, Binding Sites, COS Cells, Cell Line, Transformed, Chromosome Mapping, DNA, DNA-Binding Proteins, Gene Expression, Humans, Immunoglobulin lambda-Chains, Immunophilins, Interferon Regulatory Factors, Mice, Molecular Sequence Data, Peptidylprolyl Isomerase, Protein Conformation, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Tacrolimus, Tacrolimus Binding Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation, Tumor Cells, Cultured
Immunity
Date: Feb. 01, 2000
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