SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination

21Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

Abstract

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.

Cite

CITATION STYLE

APA

Wu, X., Fukushima, H., North, B. J., Nagaoka, Y., Nagashima, K., Deng, F., … Wei, W. (2014). SCFβ-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination. Oncotarget, 5(12), 4211–4221. https://doi.org/10.18632/oncotarget.1971

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free