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Interaction of Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) and Vav3 in the Receptor Activator of Nuclear Factor κB (RANK) Signaling Complex Enhances Osteoclastogenesis.
Yu, Jiyeon; Yun, Hyeongseok; Shin, Bongjin; Kim, Yongjin; Park, Eui-Soon; Choi, Seunga; Yu, Jungeun; Amarasekara, Dulshara Sachini; Kim, Sumi; Inoue, Jun-Ichiro; Walsh, Matthew C; Choi, Yongwon; Takami, Masamichi; Rho, Jaerang.
Afiliación
  • Yu J; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Yun H; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Shin B; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Kim Y; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Park ES; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Choi S; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Yu J; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Amarasekara DS; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Kim S; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea.
  • Inoue J; the Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
  • Walsh MC; the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and.
  • Choi Y; the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, and.
  • Takami M; the Department of Biochemistry, School of Dentistry, Showa University, Shinagawaku, 142-8555, Japan.
  • Rho J; From the Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Korea, jrrho@cnu.ac.kr.
J Biol Chem ; 291(39): 20643-60, 2016 09 23.
Article en En | MEDLINE | ID: mdl-27507811
The signaling pathway downstream of stimulation of receptor activator of nuclear factor κB (RANK) by RANK ligand is crucial for osteoclastogenesis. RANK recruits TNF receptor-associated factor 6 (TRAF6) to TRAF6-binding sites (T6BSs) in the RANK cytoplasmic tail (RANKcyto) to trigger downstream osteoclastogenic signaling cascades. RANKcyto harbors an additional highly conserved domain (HCR) that also activates crucial signaling during RANK-mediated osteoclastogenesis. However, the functional cross-talk between T6BSs and the HCR in the RANK signaling complex remains unclear. To characterize the cross-talk between T6BSs and the HCR, we screened TRAF6-interacting proteins using a proteomics approach. We identified Vav3 as a novel TRAF6 binding partner and evaluated the functional importance of the TRAF6-Vav3 interaction in the RANK signaling complex. We demonstrated that the coiled-coil domain of TRAF6 interacts directly with the Dbl homology domain of Vav3 to form the RANK signaling complex independent of the TRAF6 ubiquitination pathway. TRAF6 is recruited to the RANKcyto mutant, which lacks T6BSs, via the Vav3 interaction; conversely, Vav3 is recruited to the RANKcyto mutant, which lacks the IVVY motif, via the TRAF6 interaction. Finally, we determined that the TRAF6-Vav3 interaction resulting from cross-talk between T6BSs and the IVVY motif in RANKcyto enhances downstream NF-κB, MAPK, and NFATc1 activation by further strengthening TRAF6 signaling, thereby inducing RANK-mediated osteoclastogenesis. Thus, Vav3 is a novel TRAF6 interaction partner that functions in the activation of cooperative signaling between T6BSs and the IVVY motif in the RANK signaling complex.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Sistema de Señalización de MAP Quinasas / Complejos Multiproteicos / Factor 6 Asociado a Receptor de TNF / Proteínas Proto-Oncogénicas c-vav / Receptor Activador del Factor Nuclear kappa-B Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoclastos / Sistema de Señalización de MAP Quinasas / Complejos Multiproteicos / Factor 6 Asociado a Receptor de TNF / Proteínas Proto-Oncogénicas c-vav / Receptor Activador del Factor Nuclear kappa-B Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Biol Chem Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos