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

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...

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Autores principales: YAMAMOTO, Mizuki, GOHDA, Jin, AKIYAMA, Taishin, INOUE, Jun-ichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japan Academy 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062261/
https://www.ncbi.nlm.nih.gov/pubmed/33840674
http://dx.doi.org/10.2183/pjab.97.009
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author YAMAMOTO, Mizuki
GOHDA, Jin
AKIYAMA, Taishin
INOUE, Jun-ichiro
author_facet YAMAMOTO, Mizuki
GOHDA, Jin
AKIYAMA, Taishin
INOUE, Jun-ichiro
author_sort YAMAMOTO, Mizuki
collection PubMed
description 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.
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spelling pubmed-80622612021-04-29 TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation YAMAMOTO, Mizuki GOHDA, Jin AKIYAMA, Taishin INOUE, Jun-ichiro Proc Jpn Acad Ser B Phys Biol Sci Review 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. The Japan Academy 2021-04-09 /pmc/articles/PMC8062261/ /pubmed/33840674 http://dx.doi.org/10.2183/pjab.97.009 Text en © 2021 The Japan Academy https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
YAMAMOTO, Mizuki
GOHDA, Jin
AKIYAMA, Taishin
INOUE, Jun-ichiro
TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title_full TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title_fullStr TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title_full_unstemmed TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title_short TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation
title_sort tnf receptor-associated factor 6 (traf6) plays crucial roles in multiple biological systems through polyubiquitination-mediated nf-κb activation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062261/
https://www.ncbi.nlm.nih.gov/pubmed/33840674
http://dx.doi.org/10.2183/pjab.97.009
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