Interleukin-6 signaling via four transcription factors binding palindromic enhancers of different genes.
Interferons (IFNs), as well as some interleukins, growth factors, and hormones, all induce tyrosine phosphorylation of STAT1 and additional transcription factors of similar sizes. These factors are activated to translocate to nucleus and bind to enhancers of consensus sequence TTnCnnnAA (gamma-IFN activated sequence-like enhancers). In mammary cells or hybridoma B9 cells, four distinct tyrosine-phosphorylated transcription complexes activated by interleukin-6 (IL-6) and IFN-beta were observed: pIRFA and complexes I, II, and III (of increasing electrophoretic mobility). The factors have unequal affinities for enhancers of different genes; they are activated with distinct kinetics and to different extents by IL-6 and IFNs. The pIRFA band isolated from IL-6-stimulated B9 hybridoma cells revealed three DNA-interacting components: two large subunits of 91 and 98 kDa, as well as a small component of 46 kDa not seen in other complexes analyzed. One of the large pIRFA subunits may be APRF/STAT3, since pIRFA reacted with anti-APRF antibodies as do complexes I and II. However, pIRFA did not react with antibodies to STAT1, indicating STAT1 is not the other large component of pIRFA. Complex II, which reacted to anti-acute phase response factor antibodies also reacted to anti-STAT1 antibodies, whereas complex III reacted only to anti-STAT1 and was the only complex resistant to N-ethylmaleimide. By its multimeric subunit structure and its cytokine and enhancer sequence specificities, the slowly migrating pIRFA band appears as a novel tyrosine-phosphorylated transcription complex acting on a subset of gamma-IFN activated sequence-like enhancers.
Harroch
S
S
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Revel
M
M
Chebath
J
J
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005033:Ethylmaleimide / Q000494:pharmacology; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D011817:Rabbits; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000235:genetics
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; D010750:Phosphoproteins; D014157:Transcription Factors; D000511:alpha-Macroglobulins; D014443:Tyrosine; D007371:Interferon-gamma; D004247:DNA; D005033:Ethylmaleimide