Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52

Immunity. 2000 Feb;12(2):129-40. doi: 10.1016/s1074-7613(00)80166-1.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • 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