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KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1


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Title: KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1
Authors: Narahara, Shun / Sakai, Eiko / Kadowaki, Tomoko / Yamaguchi, Yu / Narahara, Haruna / Okamoto, Kuniaki / Asahina, Izumi / Tsukuba, Takayuki
Issue Date: 5-Mar-2019
Publisher: Springer Nature
Citation: Scientific Reports, 9(1), art.no.3523; 2019
Abstract: Kelch repeat and BTB domain-containing protein 11 (KBTBD11) is a member of the KBTBD subfamily of proteins that possess a BTB domain and Kelch repeats. Despite the presence of the Kbtbd11 gene in mammalian genomes, there are few reports about KBTBD11 at present. In this study, we identified the novel protein KBTBD11 as a negative regulator of osteoclast differentiation. We found that expression of KBTBD11 increased during osteoclastogenesis. Small-interfering-RNA-mediated knockdown of KBTBD11 enhanced osteoclast formation, and markedly increased the expression of several osteoclast marker genes compared with control cells. Conversely, KBTBD11 overexpression impaired osteoclast differentiation, and decreased the expression of osteoclast marker genes. Among six major signaling pathways regulating osteoclast differentiation, KBTBD11 predominantly influenced the nuclear factor of activated T cell cytoplasmic-1 (NFATc1) pathway. Mechanistically, KBTBD11 was found to interact with an E3 ubiquitin ligase, Cullin3. Further experiments involving immunoprecipitation and treatment with MG132, a proteasome inhibitor,showed that the KBTBD11–Cullin3 promotes ubiquitination and degradation of NFATc1 by the proteasome. Considering that NFATc1 is an essential factor for osteoclast differentiation, the KBTBD11 and Cullin3 probably regulate the levels of NFATc1 through the ubiquitin-proteasome degradation system. Thus, KBTBD11 negatively modulates osteoclast differentiation by controlling Cullin3-mediated ubiquitination of NFATc1.
URI: http://hdl.handle.net/10069/38898
DOI: 10.1038/s41598-019-40240-2
Rights: © 2019, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/38898

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