Disease relevance of BCL10

• These results correlate well with the nuclear BCL10 expression pattern in both t(1;14) and t(11;18) MALT lymphomas [1].
• The expression levels of CARMA1 and BCL10 were examined immunohistochemically in 30 patients with lymphoma [2].
• Absence of BCL10 mutations in human malignant mesothelioma [3].
• Unlike MALT lymphoma, both follicular and mantle cell lymphomas generally displayed BCL10 expression compatible to their normal cell counterparts [4].
• The API2-MALT1 fusion transcript was detected in 21 of 51 (41%) cases, and was correlated with the absence of any underlying autoimmune disease, and with a normal serum lactate dehydrogenase, a "typical" histology without marked plasmacytic differentiation or an increased number of large cells, and aberrant nuclear BCL10 expression [5].

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

• We examined BCL10 protein expression in various normal tissues and B-cell lymphomas by immunohistochemistry of formalin-fixed and paraffin-embedded tissues using mouse BCL10 monoclonal antibodies [4].

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

• The CARD of the CLAN proteins binds a number of other CARD-containing proteins including caspase-1, BCL10, NOD2, and NAC [17].
• In this study, we report that Bcl10 is rapidly phosphorylated upon activation of human T cells by PMA/ionomycin- or anti-CD3 treatment, and identify Ser(138) as a key residue necessary for Bcl10 phosphorylation [18].
• In addition, Bcl10(-/-) mice show defective hepatic cytokine production after Ang II treatment [19].
• Bcl10 and Malt1 control lysophosphatidic acid-induced NF-{kappa}B activation and cytokine production [20].
• CARMA3/Bcl10/MALT1-dependent NF-{kappa}B activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells [19].

Physical interactions of BCL10

• BCL-10 may then form a complex with MALT1 in the cell [12].
• To identify upstream signaling partners of BCL10, we performed a mammalian two-hybrid analysis and identified CARD9 as a novel CARD-containing protein that interacts selectively with the CARD activation domain of BCL10 [21].
• CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD) [22].
• Co-immunoprecipitation, In vitro binding, mammalian two-hybrid, and immunostaining assays revealed that BinCARD interacted with Bcl10 through CARD [23].
• Characterization of Bcl10 as a potential transcriptional activator that interacts with general transcription factor TFIIB [24].

Regulatory relationships of BCL10

• MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10 [1].
• When expressed in cells, CARD11 and CARD14 activate NF-kappaB and induce the phosphorylation of BCL10 [25].
• Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10 [22].
• Further, expression of BinCARD inhibited Bcl10 phosphorylation induced by T cell activation signal [23].

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

• This study further supports the close interaction between the MALT1 and BCL10 proteins in the pathogenesis of MALT lymphomas and may indicate that BCL10 immunohistochemistry is a simple technique to identify those MALT lymphoma cases with an underlying genetic aberration [29].
• Genetic and biochemical experiments identified BCL10 and MALT1 as central components of an oligomerization-ubiquitinylation-phosphorylation cascade that activates the transcription factor NF-kappaB in response to antigen receptor ligation [30].
• A subset of amplified genes was checked for overexpression by means of real-time PCR, revealing the highest expression levels for BCL6 and BCL10 [28].
• BCL10 expression was immunohistochemically evaluated in all cases, whereas t(11;18)(q21;q21) reverse transcriptase polymerase chain reaction amplification was performed on 21 samples [31].
• Fluorescence in situ hybridization with the 769E11YAC and BAC 31L5 and 2H23 probes showed the breakpoint to be located proximally to BCL10 and distally to GOT1 genes on chromosomes 1p22 and 10q24, respectively [32].

References