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.
Mamane
Y
Y
Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research and Department of Microbiology, McGill University, Montreal, Canada.
Sharma
S
S
Petropoulos
L
L
Lin
R
R
Hiscott
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001665:Binding Sites; D019556:COS Cells; D002461:Cell Line, Transformed; D002874:Chromosome Mapping; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D020104:Immunophilins / Q000235:genetics / Q000378:metabolism*; D050835:Interferon Regulatory Factors; D051379:Mice; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
D004247:DNA; D004268:DNA-Binding Proteins; D007146:Immunoglobulin lambda-Chains; D020104:Immunophilins; D050835:Interferon Regulatory Factors; D019696:Peptidylprolyl Isomerase; D011518:Proto-Oncogene Proteins; D016559:Tacrolimus; D022021:Tacrolimus Binding Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4; C058028:immunomycin