TRAF6 ubiquitin ligase is essential for RANKL signaling and osteoclast differentiation
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Tumor necrosis factor receptor-associated factor 6 (TRAF6), the crucial adaptor molecule of receptor activator of NF-kappaB (RANK), plays an essential role in governing the formation of multi-nucleated osteoclasts. TRAF6 is a RING-dependent ubiquitin (Ub) ligase that in conjunction with Ubc13/Uev1A catalyzes its own auto-ubiquitination via Lys63-linked poly-Ub chains. While the receptor-adaptor function of TRAF6 in RANK signaling is well understood, the significance of its Ub ligase activity in this process remains largely unknown. In this study, we show that retroviral expression of TRAF6, but not a RING mutant of TRAF6 was able to rescue TRAF6-deficient monocytes for the activation of IKK and osteoclast differentiation by RANKL. Furthermore, a catalytically inactive Ubc13 or stable knockdown of Ubc13 significantly prevents RANK-mediated TRAF6 ubiquitination and NF-kappaB and JNK activation. These data establish a signaling cascade in which regulated Lys63-linked TRAF6 auto-ubiquitination is the critical upstream mediator of osteoclast differentiation.
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The RANKL-activated kinase cascade requires Lys63-linked TRAF-6 auto-ubiquitination and initiates transcription of AP-1, c-Fos, NF-κB, and NFATc1, the master regulator of osteoclast differentiation.
“This cascade requires Lys63-linked TRAF-6 auto-ubiquitination [22] and initiates the transcription of activator protein-1 (AP-1), c-Fos, NF-κB, and nuclear factor of activated T cells cytoplasmic calcineurin-dependent 1 (NFATc1), the master regulator of osteoclast differentiation [20,23,24].”
From Osteoclasts and Microgravity (2020) · cites this paper as [22]
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Cites
Genetic regulation of osteoclast development and function
Teitelbaum, S. L., & Ross, F. (2003) · Nature reviews genetics · doi:10.1038/nrg1122 · Cited by 1,733 · see citing works
TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signalingPreprint
Lomaga, M. A., Yeh, W., Sarosi, I., Duncan, G. S., Furlonger, C. L., Ho, A. P., Morony, S., Capparelli, C., Van, G. Y., Kaufman, S., et al. (1999) · Genes & Development · doi:10.1101/gad.13.8.1015 · Cited by 1,253 · see citing works
Ubiquitin signalling in the NF-κB pathway
Chen, Z. J. (2005) · Nature Cell Biology · doi:10.1038/ncb0805-758 · Cited by 1,184 · see citing works
TAB2 and TAB3 Activate the NF-κB Pathway through Binding to Polyubiquitin Chains
Kanayama, A., Seth, R. B., Sun, L., Ea, C.-K., Hong, M., Shaito, A. A., Chiu, Y., Deng, L., & Chen, Z. J. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.08.008 · Cited by 890 · see citing works
Distinct molecular mechanism for initiating TRAF6 signalling
Ye, H., Arron, J. R., Lamothe, B., Cirilli, M., Kobayashi, T., Shevde, N. K., Segal, D., Dzivenu, O. K., Vologodskaia, M., Yim, M., et al. (2002) · Nature · doi:10.1038/nature00888 · Cited by 665 · see citing works
Self-citationNaito, A., Azuma, S., Tanaka, S., Miyazaki, T., Takaki, S., Takatsu, K., Nakao, K., Nakamura, K., Katsuki, M., Yamamoto, T. S., et al. (1999) · Genes to Cells · doi:10.1046/j.1365-2443.1999.00265.x · Cited by 626 · see citing works
Chung, J. Y., Park, Y. C., Ye, H., & Wu, H. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.4.679 · Cited by 613 · see citing works
Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-κB activation
Wu, C.-J., Conze, D. B., Li, T., Srinivasula, S. M., & Ashwell, J. D. (2006) · Nature Cell Biology · doi:10.1038/ncb1384 · Cited by 607 · see citing works
Characterization of the Intracellular Domain of Receptor Activator of NF-κB (RANK)
Darnay, B. G., Haridas, V., Ni, J., Moore, P. A., & Aggarwal, B. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.32.20551 · Cited by 414 · see citing works
Self-citationMechanistic insight into osteoclast differentiation in osteoimmunology
Takayanagi, H. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-004-0612-6 · Cited by 413 · see citing works
Darnay, B. G., Ni, J., Moore, P. A., & Aggarwal, B. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7724 · Cited by 399 · see citing works
Self-citationLamothe, B., Besse, A., Campos, A. D., Webster, W. K., Wu, H., & Darnay, B. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609503200 · Cited by 369 · see citing works
Self-citationTRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology
Wu, H., & Arron, J. R. (2003) · BioEssays · doi:10.1002/bies.10352 · Cited by 299 · see citing works
FRS2α attenuates FGF receptor signaling by Grb2- mediated recruitment of the ubiquitin ligase Cbl
Wong, A., Lamothe, B., Lee, A., Schlessinger, J., & Lax, I. (2002) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.052138899 · Cited by 204 · see citing works
Self-citationTRAF6 -deficient mice display hypohidrotic ectodermal dysplasia
Naito, A., Yoshida, H., Nishioka, E., Satoh, M., Azuma, S., Yamamoto, T. S., Nishikawa, S., & Inoue, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132636999 · Cited by 178 · see citing works
Osteoclast signalling pathways
Blair, H. C., Robinson, L. J., & Zaidi, M. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.077 · Cited by 155 · see citing works
Polek, T. C., Talpaz, M., Darnay, B., & Spivak-Kroizman, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302518200 · Cited by 154 · see citing works
Self-citationTAK1-dependent Signaling Requires Functional Interaction with TAB2/TAB3
Besse, A., Lamothe, B., Campos, A. D., Webster, W. K., Maddineni, U., Lin, S., Wu, H., & Darnay, B. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608867200 · Cited by 145 · see citing works
Self-citationModulation of osteoclast formation
Quinn, J. M. W., & Gillespie, M. T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.076 · Cited by 120 · see citing works
Analogies between Drosophila and mammalian TRAF pathways.
Wajant, H., & Scheurich, P. (2004) · Progress in molecular and subcellular biology · doi:10.1007/978-3-642-18670-7_3 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Role of Ubiquitin in NF-κB Regulatory Pathways
Skaug, B. A., Jiang, X., & Chen, Z. J. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.070907.102750 · Cited by 471 · see citing works
CYLD: a tumor suppressor deubiquitinase regulating NF-κB activation and diverse biological processes
Sun, S.-C. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.43 · Cited by 401 · see citing works
Recent advances in osteoclast biology
Ono, T., & Nakashima, T. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1636-2 · Cited by 385 · see citing works
Novack, D. V. (2010) · Cell Research · doi:10.1038/cr.2010.159 · Cited by 319 · see citing works
Expanding role of ubiquitination in NF-κB signaling
Liu, S., & Chen, Z. J. (2010) · Cell Research · doi:10.1038/cr.2010.170 · Cited by 243 · see citing works
Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice
Paul, P. K., Gupta, S. K., Bhatnagar, S., Panguluri, S. K., Darnay, B. G., Choi, Y., & Kumar, A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201006098 · Cited by 226 · see citing works
Self-citationRole of the Helicobacter pylori ‐Induced inflammatory response in the development of gastric cancer
Lamb, A., & Chen, L. (2012) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24389 · Cited by 211 · see citing works
Deubiquitinating enzyme CYLD negatively regulates RANK signaling and osteoclastogenesis in mice
Jin, W., Chang, M., Paul, E. M., Babu, G. R., Lee, A. J., Reiley, W. W., Wright, A., Zhang, M., You, J., & Sun, S. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34257 · Cited by 195 · see citing works
TRAF ‐Mediated TNFR ‐Family Signaling
Arron, J. R., Walsh, M. C., & Choi, Y. (2002) · Current Protocols in Immunology · doi:10.1002/0471142735.im1109ds51 · Cited by 157 · see citing works
TRAF‐Mediated TNFR‐Family Signaling
Ha, H., Han, D., & Choi, Y. (2009) · Current Protocols in Immunology · doi:10.1002/0471142735.im1109ds87 · Cited by 155 · see citing works
NF-κB: master regulator of cellular responses in health and disease
Hoffmann, A., Cheng, G., & Baltimore, D. (2025) · Immunity & Inflammation · doi:10.1007/s44466-025-00014-0 · Cited by 169 · see citing works
Paul, P. K., Bhatnagar, S., Mishra, V. K., Srivastava, S., Darnay, B. G., Choi, Y., & Kumar, A. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06351-11 · Cited by 150 · see citing works
Self-citationCurrent advances in regulation of bone homeostasis
Al‐Bari, M. A. A., & Mamun, A. A. (2020) · FASEB BioAdvances · doi:10.1096/fba.2020-00058 · Cited by 148 · see citing works
Crockett, J. C., Mellis, D. J., Scott, D. I., & Helfrich, M. H. (2011) · Osteoporosis International · doi:10.1007/s00198-010-1272-8 · Cited by 143 · see citing works
TRAF6 is a critical signal transducer in IL-33 signaling pathway
Funakoshi‐Tago, M., Tago, K., Hayakawa, M., Tominaga, S., Ohshio, T., Sonoda, Y., & Kasahara, T. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.05.013 · Cited by 138 · see citing works
Roles of the TRAF6 and Pellino E3 ligases in MyD88 and RANKL signaling
Strickson, S., Emmerich, C. H., Goh, E. T. H., Zhang, J., Kelsall, I. R., Macartney, T., Hastie, C. J., Knebel, A., Peggie, M. W., Marchesi, F., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1702367114 · Cited by 120 · see citing works
Lamothe, B., Campos, A. D., Webster, W. K., Gopinathan, A., Hur, L., & Darnay, B. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802749200 · Cited by 118 · see citing works
Self-citationNing, S., Campos, A. R., Darnay, B. G., Bentz, G. L., & Pagano, J. S. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00785-08 · Cited by 114 · see citing works
Self-citationEmerging Role of Ubiquitination in Antiviral RIG-I Signaling
Maelfait, J., & Beyaert, R. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05012-11 · Cited by 102 · see citing works
Lamothe, B., Lai, Y., Xie, M., Schneider, M. D., & Darnay, B. G. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.01225-12 · Cited by 98 · see citing works
Self-citationTWEAK and TRAF6 regulate skeletal muscle atrophy
Kumar, A., Bhatnagar, S., & Paul, P. K. (2012) · Current opinion in clinical nutrition and metabolic care · doi:10.1097/mco.0b013e328351c3fc · Cited by 103 · see citing works
Ubc13: the Lys63 ubiquitin chain building machine
Hodge, C. D., Spyracopoulos, L., & Glover, J. N. M. (2016) · Oncotarget · doi:10.18632/oncotarget.10948 · Cited by 93 · see citing works
Kim, B., Lee, K. Y., & Park, B. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.06.020 · Cited by 92 · see citing works
Autoubiquitination of BCA2 RING E3 Ligase Regulates Its Own Stability and Affects Cell Migration
Amemiya, Y., Azmi, P., & Seth, A. K. (2008) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0094 · Cited by 84 · see citing works
TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis
Hindi, S. M., & Kumar, A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81655 · Cited by 77 · see citing works
Multiple myeloma–derived MMP-13 mediates osteoclast fusogenesis and osteolytic disease
Fu, J., Li, S., Feng, R., Ma, H., Sabeh, F., Roodman, G. D., Wang, J., Robinson, S. T., Guo, X.-D. E., Lund, T., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci80276 · Cited by 76 · see citing works
TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell
Meng, Q., Zheng, M., Liu, H., Song, C., Zhang, W., Yan, J., Qin, L., & Liu, X. (2012) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-012-1434-4 · Cited by 76 · see citing works
Yao, Z., Lei, W., Duan, R., Li, Y., Luo, L., & Boyce, B. F. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.771816 · Cited by 75 · see citing works
Biswas, S., Zimman, A., Gao, D., Byzova, T. V., & Podrez, E. A. (2017) · Circulation Research · doi:10.1161/circresaha.117.311069 · Cited by 75 · see citing works
CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation
Zhang, L., Wang, Y.-W., Xiao, F., Wang, S., Xing, G., Li, Y., Yin, X., Lu, K.-F., Wei, R., Fan, J., et al. (2014) · Cell Research · doi:10.1038/cr.2014.53 · Cited by 68 · see citing works
TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell
Liu, Q. M. Z., Zhang, C. S., & Liu, J. Y. Q. (2012) · Cited by 72 · see citing works
The adaptor protein p62/SQSTM1 in osteoclast signaling pathways
McManus, S., & Roux, S. (2012) · Journal of Molecular Signaling · doi:10.1186/1750-2187-7-1 · Cited by 68 · see citing works
Beristain, A. G., Narala, S., Grappa, M. A. D., & Khokha, R. (2012) · Journal of Cell Science · doi:10.1242/jcs.094029 · Cited by 64 · see citing works
Chiu, Y., Zhao, M., & Chen, Z. J. (2009) · Chemical Reviews · doi:10.1021/cr800554j · Cited by 64 · see citing works
Paget's Disease of Bone: Evidence for Complex Pathogenetic Interactions
Chung, P. Y. J., & Hul, W. V. (2011) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2011.07.005 · Cited by 63 · see citing works
Liu, L., Jin, R., Duan, J., Yang, L., Cai, Z., Zhu, W., Nie, Y., He, J. H., Xia, C., Gong, Q., et al. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.12.022 · Cited by 62 · see citing works
Li, C.-H., Xu, L.-L., Zhao, J.-X., Sun, L., Yao, Z.-Q., Deng, X.-L., Liu, R., Yang, L., Xing, R., & Liu, X.-Y. (2016) · Inflammation Research · doi:10.1007/s00011-015-0905-y · Cited by 56 · see citing works
Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
Yen, M., Hsu, P., Liao, H., Lee, B.-H., & Tsai, H.-F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0038048 · Cited by 51 · see citing works
Lin, J., Lee, D., Choi, Y., & Lee, S. Y. (2015) · Science Signaling · doi:10.1126/scisignal.2005867 · Cited by 49 · see citing works
NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor
Mori, T., Ikeda, D. D., Fukushima, T., Takenoshita, S., & Kochi, H. (2011) · Cell Cycle · doi:10.4161/cc.10.19.17176 · Cited by 48 · see citing works
Comprehending the complex connection between PKCβ, TAK1, and IKK in BCR signaling
Shinohara, H., & Kurosaki, T. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00836.x · Cited by 48 · see citing works
Joung, Y. H., Darvin, P., Kang, D. Y., Sp, N., Byun, H. J., Lee, C.-H., Lee, H., & Yang, Y. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159891 · Cited by 45 · see citing works
Wang, Q., Yao, L., Ke Cheng, X. U., Jin, H., Chen, K., Wang, Z., Liu, Q., Cao, Z., Kenny, J., Liu, Y., et al. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13942 · Cited by 42 · see citing works
Xing, L., Zhang, M., & Chen, D. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22586 · Cited by 41 · see citing works
Park, M. Y., Kim, H. S., Lee, M., Park, B., Lee, H. Y., Cho, E. B., Seong, J. Y., & Bae, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-15586-0 · Cited by 40 · see citing works
Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton
Chen, S., Grover, M., Sibai, T. A., Black, J. O., Rianon, N. J., Rajagopal, A., Munivez, E. M., Bertin, T., Dawson, B., Chen, Y., et al. (2015) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2015.02.006 · Cited by 36 · see citing works
Zhang, W., Zhuang, Y., Zhang, Y., Yang, X. S., Zhang, H., Wang, G., Yin, W., Wang, R., Zhang, Z., & Xiao, W. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.366 · Cited by 35 · see citing works
Mukhopadhyay, U., Levantovsky, S., Carusone, T. M., Gharbi, S., Stein, F., Behrends, C., & Bhogaraju, S. (2024) · Science Advances · doi:10.1126/sciadv.adp3000 · Cited by 33 · see citing works
Zhang, H., Wu, C., Matesic, L. E., Li, X., Wang, Z., Boyce, B. F., & Xing, L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442459 · Cited by 33 · see citing works
Lamothe, B., Lai, Y.-J., Hur, L., Martín‐Orozco, N., Wang, J., Campos, A. D., Xie, M., Schneider, M. D., Lockworth, C. R., Jakacky, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051228 · Cited by 34 · see citing works
Self-citationSong, D., Cao, Z., Tickner, J. C., Qiu, H., Wang, C., Chen, K., Wang, Z., Guo, C., Dong, S., & Xu, J. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.04.011 · Cited by 34 · see citing works
Hindi, S. M., Sato, S., Choi, Y., & Kumar, A. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt536 · Cited by 31 · see citing works
Pham, L. V., Zhou, H. S., Lin-Lee, Y.-C., Tamayo, A. T., Yoshimura, L. C., Fu, L., Darnay, B. G., & Ford, R. J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706307200 · Cited by 32 · see citing works
Self-citationCell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma
Xu, L., Mohammad, K. S., Wu, H., Crean, C., Poteat, B. A., Cheng, Y., Cardoso, A. A., Machal, C., Hanenberg, H., Abonour, R., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0517 · Cited by 31 · see citing works
Jin, H., Wang, Q., Chen, K., Ke Cheng, X. U., Pan, H., Chu, F., Ye, Z., Wang, Z., Tickner, J. C., Qiu, H., et al. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14713 · Cited by 29 · see citing works
Xie, Z., Wu, Y., Shen, Y., Guo, J., Yuan, P., Ma, Q., Wang, S., Jie, Z., Zhou, H., Fan, S., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0325-1 · Cited by 28 · see citing works
Morita, Y., Ono, A., Serizawa, A., Yogo, K., Ishida‐Kitagawa, N., Takeya, T., & Ogawa, T. (2011) · Journal of Dairy Science · doi:10.3168/jds.2010-4039 · Cited by 28 · see citing works
Bishop, R. T., Marino, S., Carrasco, G., Li, B., Allen, R. J., Sparatore, A., Ottewell, P. D., Mollat, P., Sims, A. H., Capulli, M., et al. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.05.021 · Cited by 27 · see citing works
Chiou, W., Huang, Y., & Liu, Y.-W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089159 · Cited by 26 · see citing works
Wang, G., Ma, C., Chen, K., Wang, Z., Qiu, H., Chen, D., He, J., Zhang, C., Guo, D., Lai, B., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.810322 · Cited by 25 · see citing works
Osteostatin Inhibits M-CSF+RANKL-Induced Human Osteoclast Differentiation by Modulating NFATc1
Ibáñez, L., Nácher-Juan, J., Terencio, M. C., Ferrándiz, M. L., & Alcaraz, M. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158551 · Cited by 26 · see citing works
Xu, Q., Zhan, P., Li, X., Mo, F., Xu, H., Liu, Y., Lai, Q., Zhang, B., Dai, M., & Liu, X. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16949 · Cited by 22 · see citing works
Emerging role of alpha-lipoic acid in the prevention and treatment of bone loss
Roberts, J. L., & Moreau, R. F. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuu005 · Cited by 23 · see citing works
Kim, A., Kim, H. S., Lee, J. M., Choi, J. H., Kim, S. N., Kim, D. K., Kim, J. H., Mun, S. H., Kim, J. W., Jeon, H. S., et al. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.02.026 · Cited by 23 · see citing works
Coste, E., Greig, I., Mollat, P., Rose, L., Gray, M., Ralston, S., & Hof, R. J. V. '. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2013-203700 · Cited by 23 · see citing works
Wang, K., Chen, Y., Gao, S., Wang, M., Ge, M., Yang, Q., Liao, M., Xu, L., Chen, J., Zeng, Z., et al. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.09.012 · Cited by 22 · see citing works
Liu, F.-L., Chen, C., Lee, C.-C., Wu, C.-C., Hsu, T.-H., Tsai, C., Huang, H., & Chang, D. (2017) · International Journal of Medical Sciences · doi:10.7150/ijms.19268 · Cited by 21 · see citing works
Iwanowska, M., Kochman, M., Szatko, A., Zgliczyński, W., & Glinicki, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111639 · Cited by 20 · see citing works
RANKL Impairs the TLR4 Pathway by Increasing TRAF6 and RANK Interaction in Macrophages
Mota, R. F., de Araújo, P. H. C., Cezine, M. E. R., Matsuo, F. S., Metzner, R. J. M., de Biagi, C. A. O., Peronni, K. C., Hayashi, H., Shimamura, M., Nakagami, H., et al. (2022) · BioMed Research International · doi:10.1155/2022/7740079 · Cited by 18 · see citing works
Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss
Cheon, Y., Kim, J., Baek, J. M., Ahn, S., So, H., & Oh, J. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.048 · Cited by 18 · see citing works
Xie, L., Ren, X., Yang, Z., Zhou, T., Zhang, M., An, W., & Guan, Z. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.111520 · Cited by 17 · see citing works
TRAF6 negatively regulates TNFα-induced NF-κB activation
Funakoshi‐Tago, M., Kamada, N., SHIMIZU, T., Hashiguchi, Y., Tago, K., Sonoda, Y., & Kasahara, T. (2008) · Cytokine · doi:10.1016/j.cyto.2008.10.010 · Cited by 17 · see citing works
The Role of TAK1 in RANKL-Induced Osteoclastogenesis
Jianwei, W., Tian, Y., Hongwei, W., Li, D., Zou, F., Jianyuan, J., & Wang, H. (2022) · Calcified Tissue International · doi:10.1007/s00223-022-00967-z · Cited by 17 · see citing works
Yu, J., Yun, H., Shin, B., Kim, Y., Park, E.-S., Choi, S., Yu, J., Amarasekara, D. S., Kim, S., Inoue, J., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.728303 · Cited by 15 · see citing works
Swarnkar, G., Chen, T. H.-P., Arra, M., Nasir, A. M., Mbalaviele, G., & Abu‐Amer, Y. (2017) · Scientific Reports · doi:10.1038/s41598-017-12707-7 · Cited by 15 · see citing works
Marino, S., Bishop, R. T., Logan, J. G., Mollat, P., & Idris, A. I. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.09.034 · Cited by 14 · see citing works
PARK2 Induces Osteoclastogenesis through Activation of the NF-κB Pathway
Hong, S. J., Jung, S., Jang, J. S., Mo, S., Kwon, J., Kim, M. K., & Kim, H. (2022) · Molecules and Cells · doi:10.14348/molcells.2022.0058 · Cited by 13 · see citing works
ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts
Liang, X., Hou, Y., Han, L., Yu, S., Zhang, Y., Cao, X., & Yan, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.702916 · Cited by 13 · see citing works
Sumiya, E., Negishi‐Koga, T., Nagai, Y., Suematsu, A., Suda, T., Shinohara, M., Sato, K., Sanjo, H., Akira, S., & Takayanagi, H. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.06.105 · Cited by 13 · see citing works
Jeong, C., Lee, C. H., Lee, Y., Seo, J., Wang, W., Park, K.-H., Oh, E., Cho, Y., Park, J. H. Y., Son, Y., et al. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117285 · Cited by 12 · see citing works
NIP45 negatively regulates RANK ligand induced osteoclast differentiation
Shanmugarajan, S., Haycraft, C. J., Reddy, S. V., & Ries, W. L. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23460 · Cited by 12 · see citing works
Yuan, W., Hu, Y., Lu, C., Zhang, J., Li, X., Li, X., Jia, K., Huang, Y., Li, Z., Chen, X., et al. (2023) · Aquatic Toxicology · doi:10.1016/j.aquatox.2023.106596 · Cited by 11 · see citing works
Kim, E., Kwon, J., Lee, H.-S., Lee, S., Lee, D., & Jeong, G.-S. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01048 · Cited by 11 · see citing works
Hubshman, M. W., Basel‐Vanagaite, L., Krauss, A. C., Konen, O., Levy, Y., Garty, B. Z., Smirin‐Yosef, P., Maya, I., Lagovsky, I., Taub, E., et al. (2016) · Clinical Genetics · doi:10.1111/cge.12916 · Cited by 11 · see citing works
Li, M., Qi, Y., Wei, J., Lu, L., Zhao, X., & Zhou, L. (2017) · Tumor Biology · doi:10.1177/1010428317695966 · Cited by 10 · see citing works
Mao, K., Shu, W., Liu, L., Gu, Q., Qiu, Q., & Wu, X. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6210694 · Cited by 9 · see citing works
Cao, Q., Wang, Y., Huang, L., Wang, F., & Chen, S. (2015) · PubMed Central · Cited by 9 · see citing works
Tang, M., Chen, Y., Wu, J., Amin, A., Zhou, X., Jin, C., Chen, G., & Yu, Z. (2021) · Food & Function · doi:10.1039/d1fo02204k · Cited by 9 · see citing works
Wu, L., Liang, J., Li, J., Xu, Y., Chen, J., Su, Y., Xian, Y., Wei, J., Xu, J., Zhao, J., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174908 · Cited by 9 · see citing works
Wang, Y., Sun, C., Li, T., Xu, H. Y., Zhou, Y. J., Dan, H., Jiang, L., Zeng, X., Li, L., Li, J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101695 · Cited by 9 · see citing works
14-3-3ζ suppresses RANKL signaling by destabilizing TRAF6
Ayyasamy, R., Fan, S., Czernik, P. J., Lecka‐Czernik, B., Chattopadhyay, S., & Chakravarti, R. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107487 · Cited by 8 · see citing works
Emerging Roles of Non-proteolytic Ubiquitination in Tumorigenesis
Yin, X., Liu, Q., Liu, F., Tian, X., Yan, T., Han, J., & Jiang, S. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.944460 · Cited by 8 · see citing works
2-NPPA Mitigates Osteoclastogenesis via Reducing TRAF6-Mediated c-fos Expression
Chen, Z., Ding, M., Cho, E., Seong, J., Lee, S., & Lee, T. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.599081 · Cited by 8 · see citing works
Wu, M., Hsu, W.-B., Chen, M.-H., & Shi, C. (2022) · Biomedicines · doi:10.3390/biomedicines10102355 · Cited by 8 · see citing works
Swarnkar, G., Arra, M., Adapala, S., & Abu‐Amer, Y. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1669-7_16 · Cited by 7 · see citing works
Kim, H., Lee, S., & Lee, S. (2018) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2018.0191 · Cited by 7 · see citing works
E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration
Zeng, R., Xiong, Y., Lin, Z., Panayi, A. C., Sun, Y. T., Cao, F., & Liu, G. (2022) · Stem Cells International · doi:10.1155/2022/6948367 · Cited by 7 · see citing works
Al‐Bari, M. A. A., Hossain, S., Mia, U., & Mamun, M. A. A. (2020) · Current Drug Targets · doi:10.2174/1389450121666200719012116 · Cited by 8 · see citing works
L-Plastin Phosphorylation: Possible Regulation by a TNFR1 Signaling Cascade in Osteoclasts
Chellaiah, M. A. (2021) · Cells · doi:10.3390/cells10092432 · Cited by 7 · see citing works
- Authors
- Lamothe, B., Webster, W. K., Gopinathan, A., Besse, A., Campos, A. D., & Darnay, B. G.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Darnay, Bryant G.
- ORCID
- Campos, Alejandro D.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 359
- Issue
- 4
- Pages
- 1044-1049
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC2732028
- OpenAlex
- W2047682018
- Cited by
- 134
- References
- 20
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 5 · 2017: 10 · 2016: 7 · 2015: 10 · 2014: 5 · 2013: 6 · 2012: 15
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA016672)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR053540)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- TRAF6, RANKL signaling, osteoclastogenesis, ubiquitin ligase activity, Lys63-linked polyubiquitination, autoubiquitination, Ubc13, RING domain, IKK activation, NF-κB activation, JNK activation, monocytes
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Humans, Osteoblasts, Osteoclasts, Signal Transduction, Ubiquitin-Protein Ligase Complexes, TNF Receptor-Associated Factor 6, Mice, RANK Ligand
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