ArticleMolecular biology of the cell2009
c-Cbl and Cbl-b act redundantly to protect osteoclasts from apoptosis and to displace HDAC6 from beta-tubulin, stabilizing microtubules and podosomes.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- Sulfated Glucuronorhamnoxylan from Capsosiphon fulvescens Ameliorates Osteoporotic Bone Resorption via Inhibition of Osteoclastic Cell Differentiation and Function In Vitro and In Vivo.Marine biotechnology (New York, N.Y.) · 2022Article
- IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- KBTBD11, a novel BTB-Kelch protein, is a negative regulator of osteoclastogenesis through controlling Cullin3-mediated ubiquitination of NFATc1.Scientific reports · 2019Article
- Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules.Scientific reports · 2017Article
- Article
- Histone Deacetylases in Bone Development and Skeletal Disorders.Physiological reviews · 2015Review
- Tools of the trade: podosomes as multipurpose organelles of monocytic cells.Cellular and molecular life sciences : CMLS · 2015Review
- Podosome-regulating kinesin KIF1C translocates to the cell periphery in a CLASP-dependent manner.Journal of cell science · 2014Article
- Cytoplasmic retention of a nucleocytoplasmic protein TBC1D3 by microtubule network is required for enhanced EGFR signaling.PloS one · 2014Article
- Podosome organization drives osteoclast-mediated bone resorption.Cell adhesion & migration · 2014Review
- Microtubule dynamic instability controls podosome patterning in osteoclasts through EB1, cortactin, and Src.Molecular and cellular biology · 2014Article
- c-Cbl shRNA-expressing adenovirus sensitizes TRAIL-induced apoptosis in prostate cancer DU-145 through increases of DR4/5.Cancer gene therapy · 2013Article
- Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation.The Journal of clinical investigation · 2013Article
- E3 ubiquitin ligase-mediated regulation of bone formation and tumorigenesis.Cell death & disease · 2013Review
- The role of the e3 ligase cbl-B in murine dendritic cells.PloS one · 2013Article
- Met kinase-dependent loss of the E3 ligase Cbl in gastric cancer.The Journal of biological chemistry · 2012Article
- Signaling networks regulating leukocyte podosome dynamics and function.Cellular signalling · 2011Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
c-Cbl and Cbl-b are highly conserved adaptor proteins that participate in integrin signaling, regulating cytoskeletal organization, motility, and bone resorption. Deletion of both c-Cbl and Cbl-b in mice leads to embryonic lethality, indicating that the two proteins perform essential redundant functions. To examine the redundant actions of c-Cbl and Cbl-b in osteoclasts, we depleted c-Cbl in Cbl-b(-/-) osteoclasts by using a short hairpin RNA. Depleting both Cbl proteins disrupted both the podosome belt and the microtubule network and decreased bone-resorbing activity. Stabilizing the microtubules with paclitaxel or inhibiting histone deacetylase 6 (HDAC6), which destabilizes microtubules by deacetylating beta-tubulin, protected both the microtubule network and the podosome belt. Examination of the mechanism involved demonstrated that the conserved four-helix bundle of c-Cbl's tyrosine kinase binding domain bound to beta-tubulin, and both c-Cbl and Cbl-b displaced HDAC6. In addition to the effects on microtubules and the podosome belt, depleting both Cbls significantly increased the levels of the proapoptotic protein Bim and apoptosis relative to the levels induced by eliminating either protein alone. Thus, both c-Cbl and Cbl-b promote bone resorption via the stabilization of microtubules, allowing the formation of the podosome belt in osteoclasts, and by promoting osteoclast survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.