TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation

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  • YAMAMOTO Mizuki
    Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo
  • GOHDA Jin
    Research Center for Asian Infectious Diseases, The Institute of Medical Science, The University of Tokyo
  • AKIYAMA Taishin
    Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences
  • INOUE Jun-ichiro
    Research Platform Office, The Institute of Medical Science, The University of Tokyo

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Abstract

<p>NF-κB was first identified in 1986 as a B cell-specific transcription factor inducing immunoglobulin κ light chain expression. Subsequent studies revealed that NF-κB plays important roles in development, organogenesis, immunity, inflammation, and neurological functions by spatiotemporally regulating cell proliferation, differentiation, and apoptosis in several cell types. Furthermore, studies on the signal pathways that activate NF-κB led to the discovery of TRAF family proteins with E3 ubiquitin ligase activity, which function downstream of the receptor. This discovery led to the proposal of an entirely new signaling mechanism concept, wherein K63-ubiquitin chains act as a scaffold for the signaling complex to activate downstream kinases. This concept has revolutionized ubiquitin studies by revealing the importance of the nonproteolytic functions of ubiquitin not only in NF-κB signaling but also in a variety of other biological systems. TRAF6 is the most diverged among the TRAF family proteins, and our studies uncovered its notable physiological and pathological functions.</p>

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