STATs dimerize in the absence of phosphorylation.
Upon activation by tyrosine kinases, members of the STAT family of transcription factors form stable dimers that are able to rapidly translocate to the nucleus and bind DNA. Although crystal structures of activated, near full-length, Stat1 and Stat3 illustrate how STATs bind to DNA, they provide little insight into the dynamic regulation of STAT activity. To explore the unique structural changes Stat1 and Stat3 undergo when they become activated, full-length inactive recombinant proteins were prepared. To our surprise, even though these proteins are unable to bind DNA, our studies demonstrate that they exist as stable homodimers. Similarly, the Stat1 and Stat3 found in the cytoplasm of unstimulated cells also exhibit a dimeric structure. These observations indicate that Stat1 and Stat3 exist as stable homodimers prior to activation.
Braunstein
Jutta
J
Department of Microbiology, Columbia University, New York, New York 10032, USA.
Brutsaert
Siska
S
Olson
Rich
R
Schindler
Christian
C
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002845:Chromatography; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D007313:Insecta; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013395:Sucrose / Q000494:pharmacology; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014461:Ultracentrifugation
D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D013395:Sucrose; D004247:DNA; D011505:Protein-Tyrosine Kinases