SPI-C and STAT6 can cooperate to stimulate IgE germline transcription.
SPI-C is a novel ETS protein that is expressed in B lymphocytes. No target gene for SPI-C has so far been defined. We have performed a yeast two-hybrid screen using SPI-C as bait in order to further analyze the functional role of this orphan transcription factor. We found that SPI-C interacted specifically with the C-terminus of STAT6 in yeast. By co-immunoprecipitation in transfected COS7 cells the physical interaction between SPI-C and STAT6 was confirmed. Furthermore, this protein-protein interaction is functional since we could demonstrate that SPI-C and STAT6 stimulated IL4 induced Iepsilon transcription synergistically but only when both proteins bound to DNA. Thus, a protein interaction between SPI-C and STAT6 is the basis for a novel mechanism for regulation of IL4 induced gene expression.
Carlsson
Robert
R
Immunology Group, Lund University, BMC I:13, 22184 Lund, Sweden.
Thorell
Kaisa
K
Liberg
David
D
Leanderson
Tomas
T
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D047468:Immunoprecipitation; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D050783:Proto-Oncogene Proteins c-ets; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D020798:Two-Hybrid System Techniques
D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; C486039:SPIC protein, human; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D007073:Immunoglobulin E