BCL10 explained

B-cell lymphoma/leukemia 10 is a protein that in humans is encoded by the BCL10 gene.^{[1] [2]} Like BCL2, BCL3, BCL5, BCL6, BCL7A, and BCL9, it has clinical significance in lymphoma.

Function

Bcl10 was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to activate NF-κB. This protein is reported to interact with other CARD and coiled coil domain containing proteins including CARD9, -10, -11 and -14, which are thought to function as upstream regulators in NF-κB signaling. This protein is found to form a complex with the paracaspase MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and Bcl10 thought to synergize in the activation of NF-κB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy.^[2] Bcl10 is evolutionary conserved since cnidaria and has been shown to be functionally conserved all the way back to zebrafish.^{[3] [4]} Notably, just like the upstream CARD-CC family, Bcl10 is absent in insects and nematodes, and the correlated phylogenetic distribution of Bcl10 and CARD-CC proteins indicate a conserved complex.

Interactions

BCL10 has been shown to interact with:

• CARD10,^[5]
• CARD11,^[6]
• CARD14,^[6]
• CARD9^[7]
• CRADD,^[8]
• IKBKG,^[9]
• MALT1,^[10] and
• TRAF2.^[11]

Further reading

• Bertoni F, Cavalli F, Cotter FE, Zucca E . Genetic alterations underlying the pathogenesis of MALT lymphoma . Hematol. J. . 3 . 1 . 10–3 . 2003 . 11960389 . 10.1038/sj.thj.6200146.
• Lee WC, Balsara B, Liu Z, Jhanwar SC, Testa JR . Loss of heterozygosity analysis defines a critical region in chromosome 1p22 commonly deleted in human malignant mesothelioma . Cancer Res. . 56 . 19 . 4297–301 . 1996 . 8813110 .
• Koseki T, Inohara N, Chen S, Carrio R, Merino J, Hottiger MO, Nabel GJ, Núñez G . CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10 . J. Biol. Chem. . 274 . 15 . 9955–9961 . 1999 . 10187770 . 10.1074/jbc.274.15.9955 . free .
• Thome M, Martinon F, Hofmann K, Rubio V, Steiner V, Schneider P, Mattmann C, Tschopp J . Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates NF-kappaB transcription factor and c-Jun N-terminal kinase . J. Biol. Chem. . 274 . 15 . 9962–9968 . 1999 . 10187771 . 10.1074/jbc.274.15.9962 . free .
• Yan M, Lee J, Schilbach S, Goddard A, Dixit V . mE10, a novel caspase recruitment domain-containing proapoptotic molecule . J. Biol. Chem. . 274 . 15 . 10287–10292 . 1999 . 10187815 . 10.1074/jbc.274.15.10287 . free .
• Zhang Q, Siebert R, Yan M, Hinzmann B, Cui X, Xue L, Rakestraw KM, Naeve CW, Beckmann G, Weisenburger DD, Sanger WG, Nowotny H, Vesely M, Callet-Bauchu E, Salles G, Dixit VM, Rosenthal A, Schlegelberger B, Morris SW . Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32) . Nat. Genet. . 22 . 1 . 63–68 . 1999 . 10319863 . 10.1038/8767 . 1858018 .
• Srinivasula SM, Ahmad M, Lin JH, Poyet JL, Fernandes-Alnemri T, Tsichlis PN, Alnemri ES . CLAP, a novel caspase recruitment domain-containing protein in the tumor necrosis factor receptor pathway, regulates NF-kappaB activation and apoptosis . J. Biol. Chem. . 274 . 25 . 17946–17954 . 1999 . 10364242 . 10.1074/jbc.274.25.17946 . free .
• Apostolou S, De Rienzo A, Murthy SS, Jhanwar SC, Testa JR . Absence of BCL10 mutations in human malignant mesothelioma . Cell . 97 . 6 . 684–686 . 1999 . 10380921 . 10.1016/S0092-8674(02)09765-9 . free .
• Costanzo A, Guiet C, Vito P . c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB . J. Biol. Chem. . 274 . 29 . 20127–20132 . 1999 . 10400625 . 10.1074/jbc.274.29.20127 . free .
• Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M . Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein . J. Biol. Chem. . 275 . 15 . 11114–11120 . 2000 . 10753917 . 10.1074/jbc.275.15.11114 . free.
• Ye H, Dogan A, Karran L, Willis TG, Chen L, Wlodarska I, Dyer MJ, Isaacson PG, Du MQ . BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma . Am. J. Pathol. . 157 . 4 . 1147–1154 . 2000 . 11021819 . 1850175 . 10.1016/S0002-9440(10)64630-5 .
• Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES . CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B . J. Biol. Chem. . 275 . 52 . 41082–41086 . 2001 . 11053425 . 10.1074/jbc.C000726200 . free .
• Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM . Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma . Mol. Cell . 6 . 4 . 961–967 . 2000 . 11090634 . 10.1016/S1097-2765(05)00086-9 . free .
• Poyet JL, Srinivasula SM, Alnemri ES . vCLAP, a caspase-recruitment domain-containing protein of equine Herpesvirus-2, persistently activates the Ikappa B kinases through oligomerization of IKKgamma . J. Biol. Chem. . 276 . 5 . 3183–3187 . 2001 . 11113112 . 10.1074/jbc.C000792200 . free .
• Ruland J, Duncan GS, Elia A, del Barco Barrantes I, Nguyen L, Plyte S, Millar DG, Bouchard D, Wakeham A, Ohashi PS, Mak TW . Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure . Cell . 104 . 1 . 33–42 . 2001 . 11163238 . 10.1016/S0092-8674(01)00189-1 . 9100379 . free .
• Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J . Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B . J. Biol. Chem. . 276 . 24 . 21405–21409 . 2001 . 11259443 . 10.1074/jbc.M102488200 . free .
• Lucas PC, Yonezumi M, Inohara N, McAllister-Lucas LM, Abazeed ME, Chen FF, Yamaoka S, Seto M, Nunez G . Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway . J. Biol. Chem. . 276 . 22 . 19012–19019 . 2001 . 11262391 . 10.1074/jbc.M009984200 . free .
• Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES . 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 . J. Biol. Chem. . 276 . 15 . 11877–11882 . 2001 . 11278692 . 10.1074/jbc.M010512200 . 35815019 . free .
• Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J . Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation . FEBS Lett. . 496 . 2–3 . 121–127 . 2001 . 11356195 . 10.1016/S0014-5793(01)02414-0 . 22024213 . free .

Notes and References

1. Willis TG, Jadayel DM, Du MQ, Peng H, Perry AR, Abdul-Rauf M, Price H, Karran L, Majekodunmi O, Wlodarska I, Pan L, Crook T, Hamoudi R, Isaacson PG, Dyer MJ . Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types . Cell . 96 . 1 . 35–45 . March 1999 . 9989495 . 10.1016/S0092-8674(00)80957-5 . 1613152 . free .
2. Web site: Entrez Gene: BCL10 B-cell CLL/lymphoma 10.
3. Mazzone P, Scudiero I, Ferravante A, Paolucci M, D'Andrea LE, Varricchio E, Telesio G, De Maio C, Pizzulo M, Zotti T, Reale C, Vito P, Stilo R. Functional characterization of zebrafish. (Danio rerio) Bcl10 . PLOS ONE . 10 . 4 . e0122365 . April 2015 . 25849213 . 10.1371/journal.pone.0122365 . 4388727. 2015PLoSO..1022365M . free .
4. Staal J, Driege Y, Haegman M, Borghi A, Hulpiau P, Lievens L, Gul IS, Sundararaman S, Gonçalves A, Dhondt I, Pinzón JH, Braeckman BP, Technau U, Saeys Y, van Roy F, Beyaert R . 6 . Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions . Frontiers in Immunology . 9 . 1136 . 2018 . 29881386 . 5978004 . 10.3389/fimmu.2018.01136 . free .
5. Wang L, Guo Y, Huang WJ, Ke X, Poyet JL, Manji GA, Merriam S, Glucksmann MA, DiStefano PS, Alnemri ES, Bertin J . Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B . J. Biol. Chem. . 276 . 24 . 21405–9 . June 2001 . 11259443 . 10.1074/jbc.M102488200 . free .
6. Bertin J, Wang L, Guo Y, Jacobson MD, Poyet JL, Srinivasula SM, Merriam S, DiStefano PS, Alnemri ES . 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 . J. Biol. Chem. . 276 . 15 . 11877–82 . April 2001 . 11278692 . 10.1074/jbc.M010512200 . 35815019 . free .
7. Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL, Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES . CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-kappa B . J. Biol. Chem. . 275 . 52 . 41082–6 . Dec 2000 . 11053425 . 10.1074/jbc.C000726200 . free .
8. Lin Q, Liu Y, Moore DJ, Elizer SK, Veach RA, Hawiger J, Ruley HE . Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes . J. Immunol. . 188 . 6 . 2493–7 . 2012 . 22323537 . 3294148 . 10.4049/jimmunol.1101502 .
9. Wu CJ, Ashwell JD . NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation . Proc. Natl. Acad. Sci. U.S.A. . 105 . 8 . 3023–8 . February 2008 . 18287044 . 2268578 . 10.1073/pnas.0712313105 . 2008PNAS..105.3023W . free .
10. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM . Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma . Mol. Cell . 6 . 4 . 961–7 . October 2000 . 11090634 . 10.1016/S1097-2765(05)00086-9 . free .
11. Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M . Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein . J. Biol. Chem. . 275 . 15 . 11114–20 . April 2000 . 10753917 . 10.1074/jbc.275.15.11114 . free.