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SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation

NFκB is an inducible transcriptional factor controlled by two principal signaling cascades and plays pivotal roles in diverse physiological processes including inflammation, apoptosis, oncogenesis, immunity, and development. Activation of NFκB signaling was detected in skin of SHAPRIN-deficient mice...

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Autor principal: Liang, Yanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146465/
https://www.ncbi.nlm.nih.gov/pubmed/21829440
http://dx.doi.org/10.1371/journal.pone.0021696
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author Liang, Yanhua
author_facet Liang, Yanhua
author_sort Liang, Yanhua
collection PubMed
description NFκB is an inducible transcriptional factor controlled by two principal signaling cascades and plays pivotal roles in diverse physiological processes including inflammation, apoptosis, oncogenesis, immunity, and development. Activation of NFκB signaling was detected in skin of SHAPRIN-deficient mice and can be diminished by an NFκB inhibitor. However, in vitro studies demonstrated that SHARPIN activates NFκB signaling by forming a linear ubiquitin chain assembly complex with RNF31 (HOIP) and RBCK1 (HOIL1). The inconsistency between in vivo and in vitro findings about SHARPIN's function on NFκB activation could be partially due to SHARPIN's potential interactions with downstream molecules of NFκB pathway. In this study, 17 anti-flag immunoprecipitated proteins, including TRAF2, were identified by mass spectrum analysis among Sharpin-Flag transfected mouse fibroblasts, B lymphocytes, and BALB/c LN stroma 12 cells suggesting their interaction with SHARPIN. Interaction between SHARPIN and TRAF2 confirmed previous yeast two hybridization reports that SHARPIN was one TRAF2's partners. Furthermore, luciferase-based NFκB reporter assays demonstrated that SHARPIN negatively associates with NFκB activation, which can be partly compensated by over-expression of TRAF2. These data suggested that other than activating NFκB signaling by forming ubiquitin ligase complex with RNF31 and RBCK1, SHARPIN may also negatively associate with NFκB activation via interactions with other NFκB members, such as TRAF2.
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spelling pubmed-31464652011-08-09 SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation Liang, Yanhua PLoS One Research Article NFκB is an inducible transcriptional factor controlled by two principal signaling cascades and plays pivotal roles in diverse physiological processes including inflammation, apoptosis, oncogenesis, immunity, and development. Activation of NFκB signaling was detected in skin of SHAPRIN-deficient mice and can be diminished by an NFκB inhibitor. However, in vitro studies demonstrated that SHARPIN activates NFκB signaling by forming a linear ubiquitin chain assembly complex with RNF31 (HOIP) and RBCK1 (HOIL1). The inconsistency between in vivo and in vitro findings about SHARPIN's function on NFκB activation could be partially due to SHARPIN's potential interactions with downstream molecules of NFκB pathway. In this study, 17 anti-flag immunoprecipitated proteins, including TRAF2, were identified by mass spectrum analysis among Sharpin-Flag transfected mouse fibroblasts, B lymphocytes, and BALB/c LN stroma 12 cells suggesting their interaction with SHARPIN. Interaction between SHARPIN and TRAF2 confirmed previous yeast two hybridization reports that SHARPIN was one TRAF2's partners. Furthermore, luciferase-based NFκB reporter assays demonstrated that SHARPIN negatively associates with NFκB activation, which can be partly compensated by over-expression of TRAF2. These data suggested that other than activating NFκB signaling by forming ubiquitin ligase complex with RNF31 and RBCK1, SHARPIN may also negatively associate with NFκB activation via interactions with other NFκB members, such as TRAF2. Public Library of Science 2011-07-29 /pmc/articles/PMC3146465/ /pubmed/21829440 http://dx.doi.org/10.1371/journal.pone.0021696 Text en Yanhua Liang. http://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 author and source are properly credited.
spellingShingle Research Article
Liang, Yanhua
SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title_full SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title_fullStr SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title_full_unstemmed SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title_short SHARPIN Negatively Associates with TRAF2-Mediated NFκB Activation
title_sort sharpin negatively associates with traf2-mediated nfκb activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146465/
https://www.ncbi.nlm.nih.gov/pubmed/21829440
http://dx.doi.org/10.1371/journal.pone.0021696
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