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

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.

• Authors: Y Mamane, S Sharma, L Petropoulos, R Lin, J Hiscott
• Journal: Immunity (Immunity) Vol. 12 Issue 2 Pg. 129-40 (Feb 2000) ISSN: 1074-7613 [Print] United States
• PMID: 10714679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• Immunoglobulin lambda-Chains
• Interferon Regulatory Factors
• Proto-Oncogene Proteins
• Trans-Activators
• Transcription Factors
• interferon regulatory factor-4
• proto-oncogene protein Spi-1
• DNA
• immunomycin
• Tacrolimus Binding Proteins
• Immunophilins
• Peptidylprolyl Isomerase
• Tacrolimus

Topics

• Amino Acid Sequence
• Animals
• B-Lymphocytes (cytology)
• Binding Sites
• COS Cells
• Cell Line, Transformed
• Chromosome Mapping
• DNA (metabolism)
• DNA-Binding Proteins (chemistry, genetics, metabolism)
• Gene Expression (drug effects)
• Humans
• Immunoglobulin lambda-Chains (genetics)
• Immunophilins (genetics, metabolism)
• Interferon Regulatory Factors
• Mice
• Molecular Sequence Data
• Peptidylprolyl Isomerase (genetics, metabolism)
• Protein Conformation
• Protein Processing, Post-Translational
• Proto-Oncogene Proteins (genetics)
• Tacrolimus (analogs & derivatives, pharmacology)
• Tacrolimus Binding Proteins
• Trans-Activators (genetics)
• Transcription Factors (chemistry, genetics, metabolism)
• Transcriptional Activation
• Tumor Cells, Cultured