Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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B-Lymphocytes / cytology
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Binding Sites
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COS Cells
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Cell Line, Transformed
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Chromosome Mapping
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DNA / metabolism
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression / drug effects
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Humans
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Immunoglobulin lambda-Chains / genetics
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Immunophilins / genetics
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Immunophilins / metabolism*
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Interferon Regulatory Factors
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Mice
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Molecular Sequence Data
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Peptidylprolyl Isomerase / genetics
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Peptidylprolyl Isomerase / metabolism
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Protein Conformation
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Protein Processing, Post-Translational*
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Proto-Oncogene Proteins / genetics
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Tacrolimus / analogs & derivatives
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Tacrolimus / pharmacology
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Tacrolimus Binding Proteins
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Trans-Activators / genetics
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Immunoglobulin lambda-Chains
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Interferon Regulatory Factors
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Proto-Oncogene Proteins
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Trans-Activators
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Transcription Factors
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interferon regulatory factor-4
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proto-oncogene protein Spi-1
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DNA
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immunomycin
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Tacrolimus Binding Proteins
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Immunophilins
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Peptidylprolyl Isomerase
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Tacrolimus