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SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination

CYLD negatively regulates the NF-κB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor-associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells. CYLD activity is controlled by IκB kinase (IKK), but the molecular mechanism(...

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Autores principales: Wu, Xiaomian, Fukushima, Hidefumi, North, Brian J., Nagaoka, Yoshiyuki, Nagashima, Katsuyuki, Deng, Feng, Okabe, Koji, Inuzuka, Hiroyuki, Wei, Wenyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147317/
https://www.ncbi.nlm.nih.gov/pubmed/24961988
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author Wu, Xiaomian
Fukushima, Hidefumi
North, Brian J.
Nagaoka, Yoshiyuki
Nagashima, Katsuyuki
Deng, Feng
Okabe, Koji
Inuzuka, Hiroyuki
Wei, Wenyi
author_facet Wu, Xiaomian
Fukushima, Hidefumi
North, Brian J.
Nagaoka, Yoshiyuki
Nagashima, Katsuyuki
Deng, Feng
Okabe, Koji
Inuzuka, Hiroyuki
Wei, Wenyi
author_sort Wu, Xiaomian
collection PubMed
description CYLD negatively regulates the NF-κB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor-associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells. CYLD activity is controlled by IκB kinase (IKK), but the molecular mechanism(s) governing CYLD protein stability remains largely undefined. Here, we report that SCF(β-TRCP) regulates the ubiquitination and degradation of CYLD, a process dependent on prior phosphorylation of CYLD at Ser432/Ser436 by IKK. Furthermore, depletion of β-TRCP induced CYLD accumulation and TRAF6 deubiquitination in osteoclast precursor cells, leading to suppression of RANKL-induced osteoclast differentiation. Therefore, these data pinpoint the IKK/β-TRCP/CYLD signaling pathway as an important modulator of osteoclastogenesis.
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spelling pubmed-41473172014-08-29 SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination Wu, Xiaomian Fukushima, Hidefumi North, Brian J. Nagaoka, Yoshiyuki Nagashima, Katsuyuki Deng, Feng Okabe, Koji Inuzuka, Hiroyuki Wei, Wenyi Oncotarget Research Paper CYLD negatively regulates the NF-κB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor-associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells. CYLD activity is controlled by IκB kinase (IKK), but the molecular mechanism(s) governing CYLD protein stability remains largely undefined. Here, we report that SCF(β-TRCP) regulates the ubiquitination and degradation of CYLD, a process dependent on prior phosphorylation of CYLD at Ser432/Ser436 by IKK. Furthermore, depletion of β-TRCP induced CYLD accumulation and TRAF6 deubiquitination in osteoclast precursor cells, leading to suppression of RANKL-induced osteoclast differentiation. Therefore, these data pinpoint the IKK/β-TRCP/CYLD signaling pathway as an important modulator of osteoclastogenesis. Impact Journals LLC 2014-05-14 /pmc/articles/PMC4147317/ /pubmed/24961988 Text en Copyright: © 2014 Wu et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
spellingShingle Research Paper
Wu, Xiaomian
Fukushima, Hidefumi
North, Brian J.
Nagaoka, Yoshiyuki
Nagashima, Katsuyuki
Deng, Feng
Okabe, Koji
Inuzuka, Hiroyuki
Wei, Wenyi
SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title_full SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title_fullStr SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title_full_unstemmed SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title_short SCF(β-TRCP) regulates osteoclastogenesis via promoting CYLD ubiquitination
title_sort scf(β-trcp) regulates osteoclastogenesis via promoting cyld ubiquitination
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147317/
https://www.ncbi.nlm.nih.gov/pubmed/24961988
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