TRAF6 negatively regulates TNFα-induced NF-κB activation

Megumi Funakoshi-Tago, Noriyuki Kamada, Taeko Shimizu, Yusuke Hashiguchi, Kenji Tago, Yoshiko Sonoda, Tadashi Kasahara

研究成果: Article査読

14 被引用数 (Scopus)


TNF receptor-associated factor 6 (TRAF6) is an essential adaptor protein for the Interleukin-1 (IL-1) signaling pathway; however, its role in the signaling of another proinflammatory cytokine, tumor necrosis factor α (TNFα, has not been explored. Interestingly, we observed that TNFα-induced expression of IL-6, CXCL1 and granulocyte macrophage colony stimulating factor (GM-CSF) were significantly enhanced in TRAF6-deficient MEFs. Compared to those observed in wild-type MEFs, TNFα-induced IκB kinase (IKK) activation and IκBα degradation were enhanced in TRAF6-deficient MEFs. Also, TNFα-induced DNA binding activity and transcriptional activation of nuclear factor kappaB (NF-κB) were also augmented in TRAF6-deficient MEFs. On the other hand, TRAF6 deficiency did not affect the TNFα-induced activation of mitogen-activated protein (MAP) kinases, ERK, JNK, and p38. Moreover, the reintroduction of exogenous TRAF6 into TRAF6-deficient MEFs clearly suppressed TNFα-induced IKK activation, NF-κB activation and subsequent cytokine expression. In contrast, both the deletion mutant (ΔN) and the point mutant (C70A) of TRAF6, which is defective in its ubiquitin ligase activity, failed to repress TNFα-induced IKK activation, NF-κB activation and cytokine production. Thus, these data suggest that TRAF6 negatively regulates TNFα-induced NF-κB activation through its ubiquitin ligase activity.

出版ステータスPublished - 2009 2月

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 生化学
  • 血液学
  • 分子生物学


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