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BCL10  -  B-cell CLL/lymphoma 10

Homo sapiens

Synonyms: B-cell lymphoma/leukemia 10, Bcl-10, CARD-containing molecule enhancing NF-kappa-B, CARD-like apoptotic protein, CARMEN, ...
 
 
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Disease relevance of BCL10

 

Psychiatry related information on BCL10

  • Considerable evidence documents that young children evidence significant psychopathology (cf., Del Carmen & Carter, in press; Emde, 1999; Zeanah, 2001; Zeanah et al., 1997) [6].
 

High impact information on BCL10

  • Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32) [7].
  • Mutant BCL10 overexpression might have a twofold lymphomagenic effect: loss of BCL10 pro-apoptosis may confer a survival advantage to MALT B-cells, and constitutive NF-kappaB activation may provide both anti-apoptotic and proliferative signals mediated via its transcriptional targets [7].
  • Wild-type BCL10 activated NF-kappaB but induced apoptosis of MCF7 and 293 cells [7].
  • Lack of BCL10 mutations in germ cell tumors and B cell lymphomas [8].
  • Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein [9].
 

Chemical compound and disease context of BCL10

 

Biological context of BCL10

  • The CARD domain protein BCL10 and paracaspase MALT1 are essential for the activation of IkappaB kinase (IKK) and NF-kappaB in response to T cell receptor (TCR) stimulation [10].
  • It was also found that MALT1 was involved in the nuclear export of BCL10, which is originally localized in both nucleus and cytoplasm [1].
  • Another gene involved in the regulation of apoptosis, the BCL10 gene, has been cloned from a MALT lymphoma cytogenetically characterized by the t(1;14)(p22;q32) [11].
  • The t(1;14)(p22;q32), which is uncommon, juxtaposes the bcl-10 gene on chromosome 1p22 adjacent to the immunoglobulin heavy chain (IgH) gene on chromosome 14, wherein BCL10 is overexpressed via the influence of the IgH enhancer [12].
  • Furthermore, BCL10/MALT1- and API2-MALT1-induced NF-kappaB activation may contribute to anti-apoptotic action probably through NF-kappaB-mediated upregulation of apoptotic inhibitor genes [13].
 

Anatomical context of BCL10

  • The nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor kappaB (NF-kappaB) pathway but also in other biologic functions in lymphocytes [1].
  • We report here that CARD10 is a novel BCL10 interactor that belongs to the membrane-associated guanylate kinase family, a class of proteins that function to organize signaling complexes at plasma membranes [14].
  • Recent biochemical and genetic studies have clearly shown that BCL10 and MALT1 form a physical and functional complex and are both required for NF-kappaB activation by antigen receptor stimulation in T and B lymphocytes [13].
  • cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas [15].
  • Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%) [16].
 

Associations of BCL10 with chemical compounds

 

Physical interactions of BCL10

 

Regulatory relationships of BCL10

 

Other interactions of BCL10

  • Strikingly, only these oligomeric forms of BCL10 and MALT1 can activate IKK in vitro [10].
  • The positive rates for CARD9, Bcl10, and API2-MALT1 chimeric transcript in the lymphoma patients were 48%, 98%, and 8%, respectively, whereas the 3 molecules were not detected in any specimens from patients with chronic gastritis [2].
  • Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFkappaB activation [26].
  • Taken together these results support the hypothesis that enhanced BCL10 expression caused by translocation to the IGH locus can promote formation of MALT lymphomas [27].
  • Other amplifications also affected genes for which a pathogenetic role in pancreatic carcinoma has not been described, such as BCL10 and BCL6, two members of the BCL family [28].
 

Analytical, diagnostic and therapeutic context of BCL10

References

  1. MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Nakagawa, M., Hosokawa, Y., Yonezumi, M., Izumiyama, K., Suzuki, R., Tsuzuki, S., Asaka, M., Seto, M. Blood (2005) [Pubmed]
  2. Overexpression of caspase recruitment domain (CARD) membrane-associated guanylate kinase 1 (CARMA1) and CARD9 in primary gastric B-cell lymphoma. Nakamura, S., Nakamura, S., Matsumoto, T., Yada, S., Hirahashi, M., Suekane, H., Yao, T., Goda, K., Iida, M. Cancer (2005) [Pubmed]
  3. Absence of BCL10 mutations in human malignant mesothelioma. Apostolou, S., De Rienzo, A., Murthy, S.S., Jhanwar, S.C., Testa, J.R. Cell (1999) [Pubmed]
  4. BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma. Ye, H., Dogan, A., Karran, L., Willis, T.G., Chen, L., Wlodarska, I., Dyer, M.J., Isaacson, P.G., Du, M.Q. Am. J. Pathol. (2000) [Pubmed]
  5. API2-MALT1 fusion defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Okabe, M., Inagaki, H., Ohshima, K., Yoshino, T., Li, C., Eimoto, T., Ueda, R., Nakamura, S. Am. J. Pathol. (2003) [Pubmed]
  6. Assessment of young children's social-emotional development and psychopathology: recent advances and recommendations for practice. Carter, A.S., Briggs-Gowan, M.J., Davis, N.O. Journal of child psychology and psychiatry, and allied disciplines. (2004) [Pubmed]
  7. Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Zhang, Q., Siebert, R., Yan, M., Hinzmann, B., Cui, X., Xue, L., Rakestraw, K.M., Naeve, C.W., Beckmann, G., Weisenburger, D.D., Sanger, W.G., Nowotny, H., Vesely, M., Callet-Bauchu, E., Salles, G., Dixit, V.M., Rosenthal, A., Schlegelberger, B., Morris, S.W. Nat. Genet. (1999) [Pubmed]
  8. Lack of BCL10 mutations in germ cell tumors and B cell lymphomas. Fakruddin, J.M., Chaganti, R.S., Murty, V.V. Cell (1999) [Pubmed]
  9. The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway. Blonska, M., Pappu, B.P., Matsumoto, R., Li, H., Su, B., Wang, D., Lin, X. Immunity (2007) [Pubmed]
  10. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Sun, L., Deng, L., Ea, C.K., Xia, Z.P., Chen, Z.J. Mol. Cell (2004) [Pubmed]
  11. Genetic abnormalities in marginal zone B-cell lymphoma. Dierlamm, J., Wlodarska, I., Michaux, L., Stefanova, M., Hinz, K., Van Den Berghe, H., Hagemeijer, A., Hossfeld, D.K. Hematological oncology. (2000) [Pubmed]
  12. Marginal-zone B-cell lymphoma of extranodal mucosa-associated lymphoid tissue type: molecular genetics provides new insights into pathogenesis. Vega, F., Medeiros, L.J. Advances in anatomic pathology. (2001) [Pubmed]
  13. Anti-apoptotic action of API2-MALT1 fusion protein involved in t(11;18)(q21;q21) MALT lymphoma. Hosokawa, Y. Apoptosis (2005) [Pubmed]
  14. Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. Wang, L., Guo, Y., Huang, W.J., Ke, X., Poyet, J.L., Manji, G.A., Merriam, S., Glucksmann, M.A., DiStefano, P.S., Alnemri, E.S., Bertin, J. J. Biol. Chem. (2001) [Pubmed]
  15. cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. Hu, S., Du, M.Q., Park, S.M., Alcivar, A., Qu, L., Gupta, S., Tang, J., Baens, M., Ye, H., Lee, T.H., Marynen, P., Riley, J.L., Yang, X. J. Clin. Invest. (2006) [Pubmed]
  16. T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Liu, H., Ye, H., Dogan, A., Ranaldi, R., Hamoudi, R.A., Bearzi, I., Isaacson, P.G., Du, M.Q. Blood (2001) [Pubmed]
  17. CLAN, a novel human CED-4-like gene. Damiano, J.S., Stehlik, C., Pio, F., Godzik, A., Reed, J.C. Genomics (2001) [Pubmed]
  18. Bcl10 Controls TCR- and Fc{gamma}R-Induced Actin Polymerization. Rueda, D., Gaide, O., Ho, L., Lewkowicz, E., Niedergang, F., Hailfinger, S., Rebeaud, F., Guzzardi, M., Conne, B., Thelen, M., Delon, J., Ferch, U., Mak, T.W., Ruland, J., Schwaller, J., Thome, M. J. Immunol. (2007) [Pubmed]
  19. CARMA3/Bcl10/MALT1-dependent NF-{kappa}B activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. McAllister-Lucas, L.M., Ruland, J., Siu, K., Jin, X., Gu, S., Kim, D.S., Kuffa, P., Kohrt, D., Mak, T.W., Nu??ez, G., Lucas, P.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  20. Bcl10 and Malt1 control lysophosphatidic acid-induced NF-{kappa}B activation and cytokine production. Klemm, S., Zimmermann, S., Peschel, C., Mak, T.W., Ruland, J. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  21. CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B. Bertin, J., Guo, Y., Wang, L., Srinivasula, S.M., Jacobson, M.D., Poyet, J.L., Merriam, S., Du, M.Q., Dyer, M.J., Robison, K.E., DiStefano, P.S., Alnemri, E.S. J. Biol. Chem. (2000) [Pubmed]
  22. CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation. Gaide, O., Favier, B., Legler, D.F., Bonnet, D., Brissoni, B., Valitutti, S., Bron, C., Tschopp, J., Thome, M. Nat. Immunol. (2002) [Pubmed]
  23. Inhibition of Bcl10-mediated activation of NF-kappa B by BinCARD, a Bcl10-interacting CARD protein. Woo, H.N., Hong, G.S., Jun, J.I., Cho, D.H., Choi, H.W., Lee, H.J., Chung, C.W., Kim, I.K., Jo, D.G., Pyo, J.O., Bertin, J., Jung, Y.K. FEBS Lett. (2004) [Pubmed]
  24. Characterization of Bcl10 as a potential transcriptional activator that interacts with general transcription factor TFIIB. Liu, Y., Dong, W., Chen, L., Zhang, P., Qi, Y. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  25. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. Bertin, J., Wang, L., Guo, Y., Jacobson, M.D., Poyet, J.L., Srinivasula, S.M., Merriam, S., DiStefano, P.S., Alnemri, E.S. J. Biol. Chem. (2001) [Pubmed]
  26. Distinct comparative genomic hybridisation profiles in gastric mucosa-associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21). Zhou, Y., Ye, H., Martin-Subero, J.I., Hamoudi, R., Lu, Y.J., Wang, R., Siebert, R., Shipley, J., Isaacson, P.G., Dogan, A., Du, M.Q. Br. J. Haematol. (2006) [Pubmed]
  27. Bcl10 can promote survival of antigen-stimulated B lymphocytes. Tian, M.T., Gonzalez, G., Scheer, B., DeFranco, A.L. Blood (2005) [Pubmed]
  28. Genomic DNA-chip hybridization reveals a higher incidence of genomic amplifications in pancreatic cancer than conventional comparative genomic hybridization and leads to the identification of novel candidate genes. Holzmann, K., Kohlhammer, H., Schwaenen, C., Wessendorf, S., Kestler, H.A., Schwoerer, A., Rau, B., Radlwimmer, B., Döhner, H., Lichter, P., Gress, T., Bentz, M. Cancer Res. (2004) [Pubmed]
  29. MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells. Sagaert, X., Laurent, M., Baens, M., Wlodarska, I., De Wolf-Peeters, C. Mod. Pathol. (2006) [Pubmed]
  30. The Bcl10/Malt1 signaling pathway as a drug target in lymphoma. Jost, P., Peschel, C., Ruland, J. Current drug targets. (2006) [Pubmed]
  31. Aberrant nuclear BCL10 expression and lack of t(11;18)(q21;q21) in primary cutaneous marginal zone B-cell lymphoma. Gallardo, F., Bellosillo, B., Espinet, B., Pujol, R.M., Estrach, T., Servitje, O., Romagosa, V., Barranco, C., Boluda, S., García, M., Solé, F., Ariza, A., Serrano, S. Hum. Pathol. (2006) [Pubmed]
  32. Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes. Lambert, I., Debiec-Rychter, M., Guelinckx, P., Hagemeijer, A., Sciot, R. Virchows Arch. (2001) [Pubmed]
 
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