肿瘤坏死因子受体相关因子6与骨代谢的研究进展
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摘要
TRAF6是肿瘤坏死因子受体相关因子家族(TRAFs)中既可与肿瘤坏死因子受体(TNFR)超家族结合,又可与白细胞介素-1受体/Toll样受体(IL-1R/TLR)超家族相互作用来传递细胞外信号的一种细胞内接头蛋白,在炎症反应、免疫应答、骨代谢中发挥着重要作用。本文现就TRAF6在骨代谢中的研究进展作一综述。
TRAF6 is a member of TRAF family,which serves as an adapter coupling for the TNF receptor(TNFR) superfamily in intracellular signaling events.Moreover,TRAF6 is unique for signaling downstream of another receptor family,the interleukin-1(IL-1) receptor/Toll4 ike receptor(IL-1R/TLR) superfamily,which plays critical roles in inflammation and innate and adaptive immune responses.TRAF6 regulates inflammation and links immunity to bone metabolism.This paper reviews the current studies in TRAF6 on bone metabolism.
TRAF6 is a member of TRAF family,which serves as an adapter coupling for the TNF receptor(TNFR) superfamily in intracellular signaling events.Moreover,TRAF6 is unique for signaling downstream of another receptor family,the interleukin-1(IL-1) receptor/Toll4 ike receptor(IL-1R/TLR) superfamily,which plays critical roles in inflammation and innate and adaptive immune responses.TRAF6 regulates inflammation and links immunity to bone metabolism.This paper reviews the current studies in TRAF6 on bone metabolism.
引文
[1]Xie P.TRAF molecules in cell signaling and in human diseases.J Mol Signal,2013,8(1):7.
[2]Ye H,Arron JR,Lamothe B,et al.Distinct molecular mechanism for initiating TRAF6 signalling.Nature,2002,418(6896):443-447.
[3]Chung JY,Park YC,Ye H,et al.All TRAFs are not created equal:common and distinct molecular mechanisms of TRAFmediated signal transduction.J Cell Sci,2002,115(4),679-688.
[4]Zotti T,Vito P.The seventh ring:exploring TRAF7 functions.J Cell Physiol,2012,227,1280-1284.
[5]Wang Y,Zhang P,Liu Y,et al.TRAF-mediated regulation of immune and inflammatory responses.Sci China Life Sci,2010,53:159-168.
[6]Ishida T,Mizushima S,Azuma S,et al.Identification of TRAF6,a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region.J Biol Chem,1996,15,271(46):28745-28748.
[7]Cao Z,Xiong J,Takeuchi M,et al.TRAF6 is a signal transducer for interleukin-1.Nature,1996,383(6599),443-446.
[8]Wu H,Arron JR.TRAF6,a molecular bridge spanning adaptive immunity,innate immunity and osteoimmunology.Bioessays,2003,25(11):1096-1105.
[9]Chung JY,Lu M,Yin Q,et al.Molecular basis for the unique specificity of TRAF6.Adv Exp Med Biol,2007,597:122-130.
[10]Inoue J,Ishida T,Tsukamoto N,et al.Tumor necrosis factor receptor-associated factor(TRAF)family:adapter proteins that mediate cytokine signaling.Exp Cell Res,2000,254(1):14-24.
[11]Ikeda K,Takeshita S.The role of osteoclast differentiation and function in skeletal homeostasis.J Biochem,2016,159(1):1-8.
[12]Walsh MC,Choi Y.Biology of the RANKL-RANK-OPG System in Immunity,Bone,and Beyond.Front Immunol,2014,20(5):511.
[13]Armstrong AP,Tometsko ME,Glaccum M,et al.A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function.J Biol Chem,2002,277(46):44347-44356.
[14]Kadono Y,Okada F,Perchonock C,et al.Strength of TRAF6signalling determines osteoelastogenesis.EMBO Rep,2005,6(2):171-176.
[15]Kobayashi N,Kadono Y,Naito A,et al.Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis.EMBO J,2001,20(6):1271-1280.
[16]Lamothe B,Lai Y,Xie M,et al.TAK1 is essential for osteoclast differentiation and is an important modulator of cell death by apoptosis and necroptosis.Mol Cell Biol,2013,33(3):582-595.
[17]Ikeda F,Matsubara T,Tsurukai T,et al.JNK/c-Jun signaling mediates an anti-apoptotic effect of RANKL in osteoclasts.J Bone Miner Res,2008,23(6):907-914.
[18]Lee K,Chung YH,Ahn H,et al.Selective regulation of MAPK signaling mediates RANKL-dependent osteoclast differentiation.Int J Biol Sci,2016,12(2):235-245.
[19]Tomomura M,Suzuki R,Shirataki Y,et al.Rhinacanthin C inhibits osteoclast differentiation and bone resorption:roles of TRAF6/TAK1/MAPKs/NF-κB/NFATc1 signaling.PLo S One,2015,10(6):e0130174.
[20]Yen ML,Hsu PN,Liao HJ,et al.TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand(TRAIL)induces osteoclast differentiation.PLo S One,2012,7(6):e38048.
[21]Nakamura I,Kadono Y,Takayanagi H,et al.IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptorassociated factor 6/c-Src complex.J Immunol,2002,168(10):5103-5109.
[22]Maruyama K,Kawagoe T,Kondo T,et al.TRAF family member-associated NF-κB activator(TANK)is a negative regulator of osteoclastogenesis and bone formation.J Biol Chem,2012,287(34):29114-29124.
[23]Xing L,Carlson L,Story B,et al.Expression of either NFkappa B p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption.J Bone Miner Res,2003,18(2):260-269.
[24]Nishimura R.Bone and calcium update;bone research update.Regulatory mechanisms in osteoblast differentiation.Clin Calcium,2011,21(12):103-112.
[25]Chau JF,Jia D,Wang Z,et al.A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response.Nat Commun,2012,15(3):836.
[26]Li L,Wang J,Chau JF,et al.Smad1 stabilization and delocalization in response to the blockade of BMP activity.Cell Mol Biol Lett,2013,18(3):340-354.
[27]Yamashita M,Fatyol K,Jin C,et al.TRAF6 mediates Smadindependent activation of JNK and p38 by TGF-beta.Mol Cell,2008,31(6):918-924.
[28]Mishima K,Kitoh H,Ohkawara B,et al.Lansoprazole upregulates polyubiquitination of the TNF receptor-associated factor 6 and facilitates Runx2-mediated osteoblastogenesis.EBio Medicine,2015,2(12):2046-2061.
[29]Lomaga MA,Yeh WC,Sarosi I,et al.TRAF6 deficiency results in osteopetrosis and defective interleukin-1,CD40,and LPS signaling.Genes Dev,1999,13(8):1015-1024.
[30]李霞,肖明振,余擎,等.TRAF6在大鼠牙胚发育过程中的表达.实用口腔医学杂志,2005,21(1):75-77.Li X,Xiao MZ,Yu J,et al.The expression of TRAF6 in the process of rat tooth germ development.J Pract Stomatol,2005,21(1):75-77.
[31]Zhu LJ,Dai L,Zheng DH,et al.Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis.Arthritis Res Ther,2012,14(3):R133.
[32]朱浪静,欧阳霞,郑东辉,等.类风湿关节炎患者滑膜TRAF6表达与血清骨代谢标志物的相关性.中华医学杂志,2014,94(21):1643-1646.Zhu LJ,Ouyang X,Zheng DH,et al.Correlation of synoviuml TRAF6 expression in patients with rheumatoid arthritis and serum bone metabolic markers.Chinese Medical Journal,2014,94(21):1643-1646.
[33]Mc Manus S,Roux S.The adaptor protein p62/SQSTM1 in osteoclast signaling pathways.J Mol Signal,2012,4(7):1.
[34]Cavey J R,Ralston S H,Sheppard PW,et al.Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1cause Paget’s disease of bone.Calcif Tissue Int,2006,78(5):271-277.
[35]Rea SL,Walsh JP,Layfield R,et al.New insights into the role of sequestosome 1/p62 mutant proteins in the pathogenesis of Paget’s disease of bone.Endocr Rev,2013,34(4):501-524.
[36]Liu L,Gu H,Liu H,et al.Protective effect of resveratrol against IL-1β-induced inflammatory response on human osteoarthritic chondrocytes partly via the TLR4/My D88/NF-κB signaling pathway:an“in vitro study”.Int J Mol Sci,2014,15(4):6925-6940.
[2]Ye H,Arron JR,Lamothe B,et al.Distinct molecular mechanism for initiating TRAF6 signalling.Nature,2002,418(6896):443-447.
[3]Chung JY,Park YC,Ye H,et al.All TRAFs are not created equal:common and distinct molecular mechanisms of TRAFmediated signal transduction.J Cell Sci,2002,115(4),679-688.
[4]Zotti T,Vito P.The seventh ring:exploring TRAF7 functions.J Cell Physiol,2012,227,1280-1284.
[5]Wang Y,Zhang P,Liu Y,et al.TRAF-mediated regulation of immune and inflammatory responses.Sci China Life Sci,2010,53:159-168.
[6]Ishida T,Mizushima S,Azuma S,et al.Identification of TRAF6,a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region.J Biol Chem,1996,15,271(46):28745-28748.
[7]Cao Z,Xiong J,Takeuchi M,et al.TRAF6 is a signal transducer for interleukin-1.Nature,1996,383(6599),443-446.
[8]Wu H,Arron JR.TRAF6,a molecular bridge spanning adaptive immunity,innate immunity and osteoimmunology.Bioessays,2003,25(11):1096-1105.
[9]Chung JY,Lu M,Yin Q,et al.Molecular basis for the unique specificity of TRAF6.Adv Exp Med Biol,2007,597:122-130.
[10]Inoue J,Ishida T,Tsukamoto N,et al.Tumor necrosis factor receptor-associated factor(TRAF)family:adapter proteins that mediate cytokine signaling.Exp Cell Res,2000,254(1):14-24.
[11]Ikeda K,Takeshita S.The role of osteoclast differentiation and function in skeletal homeostasis.J Biochem,2016,159(1):1-8.
[12]Walsh MC,Choi Y.Biology of the RANKL-RANK-OPG System in Immunity,Bone,and Beyond.Front Immunol,2014,20(5):511.
[13]Armstrong AP,Tometsko ME,Glaccum M,et al.A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function.J Biol Chem,2002,277(46):44347-44356.
[14]Kadono Y,Okada F,Perchonock C,et al.Strength of TRAF6signalling determines osteoelastogenesis.EMBO Rep,2005,6(2):171-176.
[15]Kobayashi N,Kadono Y,Naito A,et al.Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis.EMBO J,2001,20(6):1271-1280.
[16]Lamothe B,Lai Y,Xie M,et al.TAK1 is essential for osteoclast differentiation and is an important modulator of cell death by apoptosis and necroptosis.Mol Cell Biol,2013,33(3):582-595.
[17]Ikeda F,Matsubara T,Tsurukai T,et al.JNK/c-Jun signaling mediates an anti-apoptotic effect of RANKL in osteoclasts.J Bone Miner Res,2008,23(6):907-914.
[18]Lee K,Chung YH,Ahn H,et al.Selective regulation of MAPK signaling mediates RANKL-dependent osteoclast differentiation.Int J Biol Sci,2016,12(2):235-245.
[19]Tomomura M,Suzuki R,Shirataki Y,et al.Rhinacanthin C inhibits osteoclast differentiation and bone resorption:roles of TRAF6/TAK1/MAPKs/NF-κB/NFATc1 signaling.PLo S One,2015,10(6):e0130174.
[20]Yen ML,Hsu PN,Liao HJ,et al.TRAF-6 dependent signaling pathway is essential for TNF-related apoptosis-inducing ligand(TRAIL)induces osteoclast differentiation.PLo S One,2012,7(6):e38048.
[21]Nakamura I,Kadono Y,Takayanagi H,et al.IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptorassociated factor 6/c-Src complex.J Immunol,2002,168(10):5103-5109.
[22]Maruyama K,Kawagoe T,Kondo T,et al.TRAF family member-associated NF-κB activator(TANK)is a negative regulator of osteoclastogenesis and bone formation.J Biol Chem,2012,287(34):29114-29124.
[23]Xing L,Carlson L,Story B,et al.Expression of either NFkappa B p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption.J Bone Miner Res,2003,18(2):260-269.
[24]Nishimura R.Bone and calcium update;bone research update.Regulatory mechanisms in osteoblast differentiation.Clin Calcium,2011,21(12):103-112.
[25]Chau JF,Jia D,Wang Z,et al.A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response.Nat Commun,2012,15(3):836.
[26]Li L,Wang J,Chau JF,et al.Smad1 stabilization and delocalization in response to the blockade of BMP activity.Cell Mol Biol Lett,2013,18(3):340-354.
[27]Yamashita M,Fatyol K,Jin C,et al.TRAF6 mediates Smadindependent activation of JNK and p38 by TGF-beta.Mol Cell,2008,31(6):918-924.
[28]Mishima K,Kitoh H,Ohkawara B,et al.Lansoprazole upregulates polyubiquitination of the TNF receptor-associated factor 6 and facilitates Runx2-mediated osteoblastogenesis.EBio Medicine,2015,2(12):2046-2061.
[29]Lomaga MA,Yeh WC,Sarosi I,et al.TRAF6 deficiency results in osteopetrosis and defective interleukin-1,CD40,and LPS signaling.Genes Dev,1999,13(8):1015-1024.
[30]李霞,肖明振,余擎,等.TRAF6在大鼠牙胚发育过程中的表达.实用口腔医学杂志,2005,21(1):75-77.Li X,Xiao MZ,Yu J,et al.The expression of TRAF6 in the process of rat tooth germ development.J Pract Stomatol,2005,21(1):75-77.
[31]Zhu LJ,Dai L,Zheng DH,et al.Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis.Arthritis Res Ther,2012,14(3):R133.
[32]朱浪静,欧阳霞,郑东辉,等.类风湿关节炎患者滑膜TRAF6表达与血清骨代谢标志物的相关性.中华医学杂志,2014,94(21):1643-1646.Zhu LJ,Ouyang X,Zheng DH,et al.Correlation of synoviuml TRAF6 expression in patients with rheumatoid arthritis and serum bone metabolic markers.Chinese Medical Journal,2014,94(21):1643-1646.
[33]Mc Manus S,Roux S.The adaptor protein p62/SQSTM1 in osteoclast signaling pathways.J Mol Signal,2012,4(7):1.
[34]Cavey J R,Ralston S H,Sheppard PW,et al.Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1cause Paget’s disease of bone.Calcif Tissue Int,2006,78(5):271-277.
[35]Rea SL,Walsh JP,Layfield R,et al.New insights into the role of sequestosome 1/p62 mutant proteins in the pathogenesis of Paget’s disease of bone.Endocr Rev,2013,34(4):501-524.
[36]Liu L,Gu H,Liu H,et al.Protective effect of resveratrol against IL-1β-induced inflammatory response on human osteoarthritic chondrocytes partly via the TLR4/My D88/NF-κB signaling pathway:an“in vitro study”.Int J Mol Sci,2014,15(4):6925-6940.