TY - JOUR
T1 - SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination
AU - Wu, Xiaomian
AU - Fukushima, Hidefumi
AU - North, Brian J.
AU - Nagaoka, Yoshiyuki
AU - Nagashima, Katsuyuki
AU - Deng, Feng
AU - Okabe, Koji
AU - Inuzuka, Hiroyuki
AU - Wei, Wenyi
PY - 2014
Y1 - 2014
N2 - 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 SCFβ-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.
AB - 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 SCFβ-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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U2 - 10.18632/oncotarget.1971
DO - 10.18632/oncotarget.1971
M3 - Article
C2 - 24961988
AN - SCOPUS:84905113491
VL - 5
SP - 4211
EP - 4221
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 12
ER -