The type I TGF-β receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner

Sorrentino, Alessandro; Thakur, Noopur; Grimsby, Susanne; Marcusson, Anders; Bülow, Verena von; Schuster, Norbert; Zhang, Shouting; Heldin, Carl‐Henrik; Landström, Maréne

doi:10.1038/ncb1780

Cited by 496 publications

(543 citation statements)

References 27 publications

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“…The TRAF6-TAK1-JNK/p38 pathway is essential in TGF-β induced apoptosis in prostate cancer cells. [19] This pathway also depends on SMAD7 as a scaffolding protein, enabling activation of p38. [20] R-SMAD-dependent pathways are also involved in apoptosis and one important regulator of apoptosis, the tumor suppressor gene Other mechanisms by which I-SMADs regulate SMAD signaling include prevention of R-SMAD/SMAD4 heteromerization by binding to SMAD4, recruitment of SMURFs to receptors leading to receptor degradation, and direct inhibition of transcriptional responses.…”

Section: Tgf-β/bmp Induced Apoptosismentioning

confidence: 99%

The role of bone morphogenetic proteins in myeloma cell survival

Holien

Sundan

2014

Cytokine & Growth Factor Reviews

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Section: Tgf-β/bmp Induced Apoptosismentioning

confidence: 99%

The role of bone morphogenetic proteins in myeloma cell survival

Holien

Sundan

2014

Cytokine & Growth Factor Reviews

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“…Mouse anti-Flag (M2, 1:5,000), rabbit anti-Flag (1:5,000) and anti-β-actin (1:5,000) antibodies were obtained from Sigma. Ubiquitination assays of endogenous or ectopically expressed MyD88 were performed as described [43][44][45] with minor modifications. Cells were transfected with the indicated plasmid, and subsequently treated with TGF-β1 in certain conditions.…”

Section: Construction Of Small Hairpin Rnas and Lentiviral Infectionmentioning

confidence: 99%

Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling

et al. 2011

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Transforming growth factor-β (TGF-β) is a potent anti-inflammatory cytokine that regulates interleukin-1 receptor and Toll-like receptor (TLR) signalling. Here we show a novel mechanism where TGF-β1-induced K48-linked polyubiquitination and degradation of the adaptor myD88 protein is dependent on the smad6 protein, but not smad7, and mediated by recruitment of the smad ubiquitin regulator factor proteins, smurf1 and smurf2, which have E3-ubiquitin ligase activity. smurf1 interaction with myD88 appears to be mediated by smad6, and smurf2 interaction by smurf1. Knockdown of endogenous smurf1 or smurf2 by RnA interference significantly suppresses the anti-inflammatory effects of TGF-β1 by preventing lipopolysaccharide-induced nF-κB nuclear translocation, resulting in de-suppression of proinflammatory gene expression. similar effects are observed on the lipoteichoic-acid-induced TLR2 pathway, which is also myD88-dependent, but not the myD88-independent TLR3 pathway. Thus, our results suggest that myD88 degradation driven by the smad6-smurf pathway is a novel mechanism for TGF-β1-mediated negative regulation of myD88-dependent pro-inflammatory signalling.

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“…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 type I TGF-β receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner

Cited by 496 publications

References 27 publications

The role of bone morphogenetic proteins in myeloma cell survival

The role of bone morphogenetic proteins in myeloma cell survival

Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling

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

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