Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II.
STAT6 is a central mediator of IL-4-induced gene responses. STAT6-mediated transcription is depend ent on the C-terminal transcription activation domain (TAD), but the mechanisms by which STAT6 activates transcription are poorly understood. Here, we have identified the staphylococcal nuclease (SN)-like domain and tudor domain containing protein p100 as a STAT6 TAD interacting protein. p100 was originally characterized as a transcriptional coactivator for Epstein-Barr virus nuclear antigen 2. STAT6 interacted with p100 in vitro and in vivo. The interaction was mediated by the TAD domain of STAT6 and the SN-like domain of p100. p100 did not affect the immediate activation events of STAT6, but enhanced STAT6-mediated transcriptional activation and the IL-4-induced Igepsilon gene transcription in human B-cell line. Finally, p100 associated with the large subunit of RNA polymerase II and was mediating interaction between STAT6 and RNA polymerase II. These findings identify p100 as a novel coactivator for STAT6 and suggest that p100 functions as a bridging factor between STAT6 and the basal transcription machinery.
Yang
Jie
J
Institute of Medical Technology, University of Tampere, FIN-33014 Tampere, Department of Clinical Microbiology, Tampere University Hospital, FIN-33521 Tampere, Finland.
Aittomäki
Saara
S
Pesu
Marko
M
Carter
Kara
K
Saarinen
Jussi
J
Kalkkinen
Nisse
N
Kieff
Elliott
E
Silvennoinen
Olli
O
D000818:Animals; D002458:Cell Fractionation; D002460:Cell Line; D004720:Endonucleases; D017930:Genes, Reporter; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D007073:Immunoglobulin E; D012319:RNA Polymerase II; D004720:Endonucleases; C095221:SND1 protein, human