Specific ablation of Stat3beta distorts the pattern of Stat3-responsive gene expression and impairs recovery from endotoxic shock.
Alternative splicing of the gene for Stat3, a transcription factor activated by the IL-6 family of cytokines, produces two isoforms: Stat3alpha and a dominant-negative variant, Stat3beta. Stat3beta-deficient mice were generated by gene targeting. Despite intact expression and phosphorylation of Stat3alpha, overall Stat3 activity was impaired in Stat3beta(-/-) cells. Global comparison of transcription in Stat3beta(+/+) and Stat3beta(-/-) cells revealed stable differences. Stat3beta-deficient mice exhibit diminished recovery from endotoxic shock and hyperresponsiveness of a subset of endotoxin-inducible genes in liver. The hepatic response to endotoxin in wild-type mice is accompanied by a transient increase in the ratio of Stat3beta to Stat3alpha. These findings indicate a critical role for Stat3beta in the control of systemic inflammation.
Yoo
Joo-Yeon
JY
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Baltimore, MD, USA.
Huso
David L
DL
Nathans
Daniel
D
Desiderio
Stephen
S
D000209:Acute-Phase Proteins / Q000235:genetics; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D004731:Endotoxins; D008099:Liver / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics; D050796:STAT3 Transcription Factor; D012772:Shock, Septic / Q000235:genetics* / Q000503:physiopathology; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D004731:Endotoxins; D020033:Protein Isoforms; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators