Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32)

Zhang, Quangeng; Siebert, Reiner; Yan, Minhong; Hinzmann, Bernd; Cui, Xiaoli; Xue, Liquan; Rakestraw, Karen M.; Naeve, Clayton W.; Beckmann, Georg; Weisenburger, Dennis D.; Sanger, Warren G.; Nowotny, H.; Vesely, Michael; Callet‐Bauchu, Evelyne; Salles, Gilles; Dixit, Vishva M.; Rosenthal, André; Schlegelberger, Brigitte; Morris, Stephan W.

doi:10.1038/8767

Cited by 360 publications

(331 citation statements)

References 24 publications

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“…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]. The Bcl10 effects appear to be mediated through its interaction with IKKγ (or Nemo), the regulatory component of the IKK signalosome.…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…t(1;14)(p22;q32) results in placement of the BCL10 gene adjacent to the strong immunoglobulin heavy-chain locus transcriptional enhancer, leading to deregulated overexpression of Bcl10 (Willis et al, 1999;Zhang et al, 1999). Similarly, t(14;18)(q32;q21) results in translocation of the MALT1 gene to the immunoglobulin heavy-chain locus and leads to MALT1 overexpression (Murga Penas et al, 2003;Streubel et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

A dual role for the API2 moiety in API2-MALT1-dependent NF-κB activation: heterotypic oligomerization and TRAF2 recruitment

Lucas

Kuffa

et al. 2007

Oncogene

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Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid neoplasm. Chromosomal translocation t(11;18)(q21,q21) is found in 30% of gastric MALT lymphomas and is associated with a failure to respond to standard treatment and a tendency to disseminate. This translocation generates a chimeric protein composed of N-terminal sequences of Inhibitor of Apoptosis 2 (API2, also known as BIRC3 and cIAP2) fused to C-terminal sequences of MALT1. API2-MALT1 promotes cell survival and proliferation via activation of nuclear factor-jB (NF-jB). Here, we investigate the mechanism by which the API2 moiety contributes to NF-jB stimulation. We find that the API2 moiety mediates oligomerization of API2-MALT1 as well as interaction with tumor necrosis factor receptor-associated factor 2 (TRAF2). Surprisingly, oligomerization does not occur via homotypic interaction; rather, the API2 moiety of one monomer interacts with the MALT1 moiety of another monomer. Further, the specific region of the API2 moiety responsible for mediating oligomerization is distinct from that mediating TRAF2 binding. Although deletion or mutation of the TRAF2 binding site does not inhibit oligomerization, it does lead to dramatically decreased NF-jB activation. Deletion of both TRAF2 binding and oligomerization regions results in nearcomplete loss of NF-jB activation. Thus, API2 moietymediated heterotypic oligomerization and TRAF2 binding both contribute to maximal API2-MALT1-dependent NF-jB stimulation.

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“…Previous studies suggest that CBM proteins are involved in lymphoma pathogenesis [30,31,41,110]. Chromosomal translocations, which lead to the overexpression of Bcl10 and MALT1 or generation of API2-MALT1 fusion protein, were found in MALT lymphoma [30,41,43], and the activation of NF-κB by these oncogenic proteins is believed to be one of the hallmarks of MALT lymphoma.…”

Section: The Role Of Cbm Proteins In Lymphomamentioning

confidence: 99%

“…Bcl10 was identified by functional cloning from mucosa-associated lymphoid tissue (MALT) lymphoma cells [30,31] and by bioinformatics approaches as a CARD-containing protein [32][33][34]. Genetic studies using Bcl10-deficient mice have revealed that Bcl10 is an essential component in the T cell receptor (TCR)-and B cell receptor (BCR)-induced NF-κB activation, and functions downstream of PKC [29,35].…”

Section: Cbm Proteins In Antigen Receptor Signalingmentioning

confidence: 99%

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

Blonska¹,

Lin²

2010

Cell Res

176

201

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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.

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Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32)

Cited by 360 publications

References 24 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

A dual role for the API2 moiety in API2-MALT1-dependent NF-κB activation: heterotypic oligomerization and TRAF2 recruitment

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

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