TAK1-dependent Signaling Requires Functional Interaction with TAB2/TAB3

Besse, Arnaud; Lamothe, Betty; Campos, Alejandro D.; Webster, William K.; Maddineni, Upendra; Lin, Su Chang; Wu, Hao; Darnay, Bryant G.

doi:10.1074/jbc.m608867200

Cited by 123 publications

(120 citation statements)

References 49 publications

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“…The WNT4 gene is the member of the Wnt ligands and has been identified as being associated with the vertebral cross-sectional area (CSA) in older Caucasian men, (22) whereas TAB2 may regulate osteoblastogenesis and the development and function of osteoclasts. (23,24) Note that the candidate gene variants for osteoporotic fracture are not simply the same as those for low BMD. (8,25) In addition to BMD, the bone matrix, bone strength, falling risk, and environmental factors take responsibility for osteoporotic fracture.…”

Section: Introductionmentioning

confidence: 99%

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Wang

Zeng

Zhang

et al. 2012

Journal of Bone and Mineral Research

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To identify the susceptibility genes for osteoporotic fracture in postmenopausal Chinese women, a two-stage case-control association study using joint analysis was conducted in 1046 patients with nontraumatic vertebra, hip, or distal radius fractures and 2303 healthy controls. First, 113 single-nucleotide polymorphisms (SNPs) in 16 potential osteoporosis candidate genes reported in recent genomewide association studies, meta-analyses studies, large-scale association studies, and functional studies were genotyped in a smallsample-size subgroup consisting of 541 patients with osteoporotic fractures and 554 healthy controls. Variants and haplotypes in SPTBN1, TNFRSF11B, CNR2, LRP4, and ESR1 that have been identified as being associated with osteoporotic fractures were further reanalyzed in the entire case-control group. We identified one SNP in TNFRSF11B (rs3102734), three SNPs in ESR1 (rs9397448, rs2234693, and rs1643821), two SNPs in LRP4 (rs17790156 and rs898604), and four SNPs in SPTBN1 (rs2971886, rs2941583, rs2941584, and rs12475342) were associated with all of the broadly defined osteoporotic fractures. The most significant polymorphism was rs3102734, with increased risk of osteoporotic fractures (odds ratio, 1.35; 95% confidence interval [CI], 1.17-1.55, Bonferroni p ¼ 2.6 Â 10 À4 ). Furthermore, rs3102734, rs2941584, rs12475342, rs9397448, rs2234693, and rs898604 exhibited significant allelic, genotypic, and/or haplotypic associations with vertebral fractures. SNPs rs12475342, rs9397448, and rs2234693 showed significant genotypic associations with hip fractures, whereas rs3102734, rs2073617, rs1643821, rs12475342, and rs2971886 exhibited significant genotypic and/or haplotypic associations with distal radius fractures. Accordingly, we suggest that in addition to the clinical risk factors, the variants in TNFRSF11B, SPTBN1, ESR1, and LRP4 are susceptibility genetic loci for osteoporotic fracture in postmenopausal Chinese women. ß

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Section: Introductionmentioning

confidence: 99%

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Wang

Zeng

Zhang

et al. 2012

Journal of Bone and Mineral Research

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“…The phosphorylation and activation of TAK1 subsequently leads to MAPKs and inhibitory κB kinase (IKK) activation, the prerequisite event necessary to induce NF-κB. In this process, TAK1-associated binding protein-2 (TAB2) acts as a bridge linking TRAF6 to TAK1 [26]. Although the mechanism by which TAK1 is activated is not fully understood, many studies have revealed the critical role of the lysine-63-linked polyubiquitination by TRAF6 in the activation of TAK1 [27,28].…”

Section: Introductionmentioning

confidence: 99%

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Cronstein

2012

Purinergic Signalling

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Adenosine is an endogenous nucleoside that modulates many physiological processes through four receptor subtypes (A 1 , A 2a , A 2b , A 3 ). Previous work from our laboratory has uncovered a critical role for adenosine A 1 receptor (A 1 R) in osteoclastogenesis both in vivo and in vitro. Our current work focuses on understanding the details of how A 1 R modulates the receptor activator of NF-κB ligand (RANKL)-induced signaling in osteoclastogenesis. Osteoclasts were generated from mouse bone marrow precursors in the presence of RANKL and macrophage-colony stimulating factor. A pharmacological antagonist of A 1 R (DPCPX) inhibited RANKL-induced osteoclast differentiation, including osteoclast-specific genes (Acp5, MMP9, β 3 Integrin, α v Integrin, and CTSK) and osteoclast-specific transcription factors such as c-fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression in a dose-dependent manner. DPCPX also inhibited RANKL-induced activation of NF-κB and JNK/ c-Jun but had little effect on other mitogen-activated protein kinases (p38 and Erk). Finally, immunoprecipitation analysis showed that blockade of A 1 R resulted in disruption of the association of tumor necrosis factor receptor-associated factor 6 (TRAF6) and transforming growth factor-β-activated kinase 1 (TAK1), a signaling event that is important for activation of NF-κB and JNK, suggesting the participation of adenosine/ A 1 R in early signaling of RANKL. Collectively, these data demonstrated an important role of adenosine, through A 1 R in RANKL-induced osteoclastogenesis.

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“…The TAB2 NZF domain has been shown to interact with K63-type, but not linear, polyubiquitin chains (15)(16)(17). TAB2 and TAB3 interact with K63-linked polyubiquitin chains and activate TAK1-mediated NF-kB activation (18,19). NEMO also has the potential to bind K63-linked polyubiquitin chains, but the affinity of NEMO for linear polyubiquitin chains seems to be even greater than for K63-linked ubiquitin chains (20,21).…”

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Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activation via MAPKs

Ori

Kato

Sanjo

et al. 2013

The Journal of Immunology

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Polyubiquitination of proteins plays a critical role in the activation of immune cells. K63-linked polyubiquitin-binding proteins TGF-β–activated kinase 1 (TAK1)–binding protein (TAB)2 and TAB3 are implicated in NF-κB signaling via TAK1 activation. However, TAB2 alone is dispensable for NF-κB activation in embryonic fibroblasts, and the functional roles of TAB2 and TAB3 in immune cells has yet to be clarified. In this study, we demonstrate that TAB2 and TAB3 are essential for B cell activation leading to Ag-specific Ab responses, as well as B-1 and marginal zone B cell development. TAB2 and TAB3 are critical for the activation of MAPKs, especially ERK, but not NF-κB, in response to TLR and CD40 stimulation in B cells. Surprisingly, TAB2 and TAB3 are dispensable for TAK1 activation in B cells, indicating that TAB2 and TAB3 activate MAPKs via a pathway independent of TAK1. In contrast to B cells, macrophages lacking TAB2 and TAB3 did not show any defects in the cytokine production and the signaling pathway in response to TLR stimulation. Furthermore, TAB2 and TAB3 were dispensable for TNF-induced cytokine production in embryonic fibroblasts. Thus, TAB2- and TAB3-mediated K63-linked polyubiquitin recognition controls B cell activation via MAPKs, but not the TAK1/NF-κB axis.

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TAK1-dependent Signaling Requires Functional Interaction with TAB2/TAB3

Cited by 123 publications

References 49 publications

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Susceptibility genes for osteoporotic fracture in postmenopausal chinese women

Adenosine A1 receptor regulates osteoclast formation by altering TRAF6/TAK1 signaling

Essential Roles of K63-Linked Polyubiquitin-Binding Proteins TAB2 and TAB3 in B Cell Activation via MAPKs

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