Bcl10 plays a critical role in NF-κB activation induced by G protein-coupled receptors

Wang, Donghai; You, Yun; Lin, Pei; Xue, Liquan; Morris, Stephan W.; Zeng, Hu; Wen, Renren; Lin, Xin

doi:10.1073/pnas.0601894104

Cited by 99 publications

(86 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent reports, including our work in human colonic epithelial cells, have also established a role for Bcl10 in an inflammatory pathway in non-immune cells, including mouse embryonic kidney cells and hepatocytes [5,8,[20][21][22]. Bcl10 is recognized as a mediator of constitutive activation of NFκB in the MALT lymphomas, in which there is a translocation involving Bcl10 [23][24][25].…”

Section: Discussionmentioning

confidence: 56%

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Bhattacharyya

Dudeja

Tobacman

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/ lymphoma 10). However, increases in phospho-IκBα and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFκB (p65), phospho-IκBα, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38γ), MAPK 13 (p38δ), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IκBα kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKγ (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome.

show abstract

Section: Discussionmentioning

confidence: 56%

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Bhattacharyya

Dudeja

Tobacman

2008

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

show abstract

“…Other reports have defined a critical role for BCL10 in the inflammatory cascade in epithelial cells, including activation by lysophosphatidic acid (3), G-protein-coupled receptor (4), and angiotensin II (5). In this report, we demonstrate that BCL10 was required for NF-B activation by both canonical and noncanonical pathways, following stimulation by the sulfated polysaccharide carrageenan (CGN) in mouse embryonic fibroblasts and in human colonic epithelial cells.…”

Section: Ikk␣mentioning

confidence: 63%

B-cell CLL/Lymphoma 10 (BCL10) Is Required for NF-κB Production by Both Canonical and Noncanonical Pathways and for NF-κB-inducing Kinase (NIK) Phosphorylation

Bhattacharyya

Borthakur

Tyagi

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The importance of activation of B-cell lymphoma/CLL 10 (BCL10) 2 has been recognized previously in the mucosa-associated lymphoid tissue (MALT) lymphomas, in which translocations involving MALT1 lead to constitutive activation of BCL10 and NF-B transcription (1, 2). Other reports have defined a critical role for BCL10 in the inflammatory cascade in epithelial cells, including activation by lysophosphatidic acid (3), G-protein-coupled receptor (4), and angiotensin II (5). In this report, we demonstrate that BCL10 was required for NF-B activation by both canonical and noncanonical pathways, following stimulation by the sulfated polysaccharide carrageenan (CGN) in mouse embryonic fibroblasts and in human colonic epithelial cells. Previously, we reported that CGN significantly up-regulated transcription of BCL10 in NCM460 cells (6, 7). The sulfated polysaccharide carrageenan has been widely used for decades to induce inflammation in animal and tissue culture models. In our previous work, CGN was shown to induce an inflammatory cascade in human colonic epithelial cells by two distinct mechanisms: an immune-mediated mechanism involving TLR4 (toll-like receptor 4), IRAK (IL-1␤ receptor activating kinase), BCL10, phospho-IB␣ (inhibitor of B), NF-B (nuclear factor B), and IL-8 (interleukin-8); and a reactive oxygen species (ROS)-mediated mechanism involving phospho-Hsp27, IB kinase (IKK)-␤, phospho-IB␣, BCL10, NF-B, and . Carrageenan activation of these pathways was attributable to its distinctive chemical structure, including its resemblance to the naturally occurring glycosaminoglycans, its highly sulfated galactose residues, and its unusual ␣-Gal(133)Gal bond that is a known immune epitope (10, 11). Because CGN is a commonly used food additive in the Western diet, these pathways may induce inflammation and disease in the human colon and implicate a role for BCL10 in human disease, in addition to the MALT lymphomas.To further define the BCL10-mediated activation of NF-B and the interactions between the ROS and TLR4-BCL10 pathways, the requirements for different components of the IKK signaling complex and the responses of different members of the NF-B family were investigated. The IKK signaling complex, including the catalytic components IKK␣ and IKK␤ and the regulatory component IKK␥, also known as NEMO (NF-B essential modifying factor), integrates upstream signals and leads to the phosphorylation of IB␣. Subsequently, phospho-IB␣ is ubiquitinated, and the localization signal for NF-B nuclear translocation is exposed. These events represent critical signals in the progression of the inflammatory cascade from * This work was supported in part by the Department of Veterans Affairs (to J. K. T.) and by NIDDK, National Institutes of Health Grants DK68324 and DK54016 (to P. K. D.

show abstract

“…Similarly to CARMA3, Bcl10-and MALT1-deficient cells have defective NF-κB activation following LPA treatment [134,135]. These results indicate that the CARMA3-Bcl10-MALT1 complex may play an analogues role in non-hematopoietic cells as the CARMA1-Bcl10-MALT1 complex in the TCR and BCR pathways in hematopoietic cells ( Figure 4A).…”

Section: Carma3-mediated Nf-κb Signaling Pathwaysmentioning

confidence: 86%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

Self Cite

176

201

View full text Add to dashboard Cite

The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

show abstract

Bcl10 plays a critical role in NF-κB activation induced by G protein-coupled receptors

Cited by 99 publications

References 26 publications

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

Carrageenan-induced NFκB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10

B-cell CLL/Lymphoma 10 (BCL10) Is Required for NF-κB Production by Both Canonical and Noncanonical Pathways and for NF-κB-inducing Kinase (NIK) Phosphorylation

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Contact Info

Product

Resources

About