Interleukin 1 activates STAT3/nuclear factor-κB cross-talk via a unique TRAF6-and p65-dependent mechanism

被引:115
作者
Yoshida, Y
Kumar, A
Koyama, Y
Peng, HB
Arman, A
Boch, JA
Auron, PE
机构
[1] Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA
关键词
D O I
10.1074/jbc.M311498200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukins (IL) 1 and 6 are important cytokines that function via the activation, respectively, of the transcription factors NF-kappaB and STAT3. We have observed that a specific type of kappaB DNA sequence motif supports both NF-kappaB p65 homodimer binding and cooperativity with non-tyrosine-phosphorylated STAT3. This activity, in contrast to that mediated by kappaB DNA motifs that do not efficiently bind p65 homodimers, is shown to be uniquely dependent upon signal transduction through the carboxyl terminus of TRAF6. Furthermore, STAT3 and p65 are shown to physically interact, in vivo, and this interaction appears to inhibit the function of "classical" STAT3 GAS-like binding sites. The distinct p50 form of NF-kappaB is also shown to interact with STAT3. However, in contrast to p65, p50 cooperates with STAT3 bound to GAS sites. These data argue for a novel transcription factor cross-talk mechanism that may help resolve inconsistencies previously reported regarding the mechanism of IL-1 inhibition of IL-6 activity during the acute-phase response.
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页码:1768 / 1776
页数:9
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