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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(...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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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. |
format | Online Article Text |
id | pubmed-4147317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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