SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination

Xiaomian Wu, Hidefumi Fukushima, Brian J. North, Yoshiyuki Nagaoka, Katsuyuki Nagashima, Feng Deng, Koji Okabe, Hiroyuki Inuzuka, Wenyi Wei

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)4211-4221
Number of pages11
Issue number12
Publication statusPublished - 2014


  • CYLD
  • Degradation
  • Phosphorylation
  • Tumor suppressor
  • Ubiquitination
  • β-TRCP

ASJC Scopus subject areas

  • Oncology

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