Last update 19 Sep 2024

BCL10

Last update 19 Sep 2024

Basic Info

Synonyms

B-cell CLL/lymphoma 10, B-cell lymphoma/leukemia 10, Bcl-10

+ [15]

Introduction

Plays a key role in both adaptive and innate immune signaling by bridging CARD domain-containing proteins to immune activation (PubMed:10187770, PubMed:10364242, PubMed:10400625, PubMed:25365219, PubMed:24074955). Acts by channeling adaptive and innate immune signaling downstream of CARD domain-containing proteins CARD9, CARD11 and CARD14 to activate NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:24074955). Recruited by activated CARD domain-containing proteins: homooligomerized CARD domain-containing proteins form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10, subsequent recruitment of MALT1 and formation of a CBM complex (PubMed:24074955). This leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:18287044, PubMed:27777308, PubMed:24074955). Activated by CARD9 downstream of C-type lectin receptors; CARD9-mediated signals are essential for antifungal immunity (PubMed:26488816). Activated by CARD11 downstream of T-cell receptor (TCR) and B-cell receptor (BCR) (PubMed:18264101, PubMed:18287044, PubMed:27777308, PubMed:24074955). Promotes apoptosis, pro-caspase-9 maturation and activation of NF-kappa-B via NIK and IKK (PubMed:10187815).

100 Clinical Results associated with BCL10

100 Translational Medicine associated with BCL10

0 Patents (Medical) associated with BCL10

760

Literatures (Medical) associated with BCL10

01 Sep 2024·Combinatorial Chemistry & High Throughput Screening

Exploration of Key Genes Combining with Immune Infiltration Level and Tumor Mutational Burden in Hepatocellular Carcinoma

Article

Author: Xu, Chen-Zhou ; Chen, Jing ; Zhang, Lu ; Lu, Cui-Hua

Background:Hepatocellular carcinoma (HCC) is a lethal malignancy due to its heterogeneity and aggressive behavior. Recently, somatic mutations and tumor cell interactions with the surrounding tumor immune microenvironment (TIME) have been reported to participate in HCC carcinogenesis and predict HCC progression. In this study, we aimed to investigate the association between tumor mutational burden (TMB) and TIME in HCC. Additionally, we sought to identify differentially expressed genes (DEGs) associated with HCC prognosis and progression.Methods:The expression, clinical, and mutational data were downloaded from the cancer genome atlas (TCGA) database. The immune infiltration levels and TMB levels of the HCC samples were estimated and the samples were divided into immune cluster (ICR)-1 and 2 based on immune infiltration score and high and low TMB groups based on TMB score. Thereafter, differential gene expression analysis was conducted to identify the DEGs in the ICR1/2 and high/low TMB groups, and the intersecting DEGs were selected. Thereafter, Cox regression analysis was performed on 89 significant DEGs, among which 19 were associated with prognosis. These 19 DEGs were then used to construct a prognostic model based on their expression levels and regression coefficients. Thereafter, we analyzed the DEGs in mutant and wildtype TP53 HCC samples and identified high BCL10 and TRAF3 expression in the mutant TP53 samples. BCL10 and TRAF3 expression was detected by real-time quantitative reverse transcription PCR and immunohistochemistry, and their clinical correlation, biological function, and immune infiltration levels were analyzed by chi-square analyses, Gene Set Enrichment Analysis (GSEA), and “ssGSEA”, respectively.Results:The results of our study revealed that immune infiltration level was correlated with TMB and that they synergistically predicted poor prognosis of HCC patients. DEGs enriched in immune-related pathways could serve as indicators of immunotherapy response in HCC. Among these DEGs, BCL10 and TRAF3 were highly expressed in HCC tissues, especially in the mutant TP53 group, and they co-operatively exhibited immunological function, thereby affecting HCC progression and prognosis.Conclusion:In this study, we identified BCL10 and TRAF3 as potential prognostic indicators in HCC patients. Additionally, we found that BCL10 and TRAF3 influence TMB and TIME in HCC patients and can be used for the development of immune-based therapies for improving the long-term survival of HCC patients.

01 Jul 2024·Chemosphere

Synergistic effect of biochar with gypsum, lime, and farm manure on the growth and tolerance in rice plants under different salt-affected soils

Article

Author: Alamri, Amnah M ; Hamoud, Yousef Alhaj ; Alabdallah, Nadiyah M ; Alharby, Hesham F ; Shaghaleh, Hiba ; Al-Sarraj, Faisal ; Rizwan, Muhammad ; Zia-Ur-Rehman, Muhammad ; Usman, Muhammad ; Saleem, Talha

Soil salinization and sodication harm soil fertility and crop production, especially in dry regions. To combat this, using biochar combined with gypsum, lime, and farm manure is a promising solution for improving salt-affected soils. In a pot experiment, cotton stick biochar (BC) was applied at a rate of 20 t/ha in combination with gypsum (G), lime (L), and farm manure (F) at rates of 5 and 10 t/ha. These were denoted as BCG-5, BCL-5, BCF-5, BCG-10, BCL-10, and BCF-10. Three different types of soils with electrical conductivity (EC) to sodium adsorption ratio (SAR) ratios of 2.45:13.7, 9.45:22, and 11.56:40 were used for experimentation. The application of BCG-10 led to significant improvements in rice biomass, chlorophyll content, and overall growth. It was observed that applying BCG-10 to soils increased the membrane stability index by 75% in EC:SAR (2.45:13.7), 97% in EC:SAR (9.45:22), and 40% in EC:SAR (11.56:40) compared to respective control treatments. After BCG-10 was applied, the hydrogen peroxide in leaves dropped by 29%, 23%, and 21% in EC:SAR (2.45:13.7), EC:SAR (9.45:22), and EC:SAR (11.56:40) soils, relative to their controls, respectively. The application of BCG-10 resulted in glycine betaine increases of 60, 119, and 165% in EC: SAR (2.45:13.7), EC: SAR (9.45:22), and EC: SAR (11.56:40) soils. EC: SAR (2.45:13.7), EC: SAR (9.45:22), and EC: SAR (11.56:40) soils all had 70, 109, and 130% more ascorbic acid in BCG-10 applied treatment, respectively. The results of this experiment show that BCG-10 increased the growth and physiological traits of rice plants were exposed to different levels of salt stress. This was achieved by lowering hydrogen peroxide levels, making plant cells more stable, and increasing non-enzymatic activity.

01 Jul 2024·Biochemical and Biophysical Research Communications

Study of individual domains contributing to MALT1 dimerization in BCL10-independent and dependent assembly

Article

Author: Huang, Po-Hui ; Tu, Yi-Fan ; Lin, Su-Chang ; Lo, Yu-Chih ; Kuo, Bai-Jiun

The CARMA-BCL10-MALT1 (CBM) signalosome functions as a pivotal supramolecular module, integrating diverse receptor-induced signaling pathways to regulate BCL10-dependent NF-kB activation in innate and adaptive immunity. Conversely, the API2-MALT1 fusion protein in t(11; 18)(q21; q21) MALT lymphoma constitutively induces BCL10-independent NF-kB activation. MALT1 dimer formation is indispensable for the requisite proteolytic activity and is critical for NF-kB activation regulation in both scenarios. However, the molecular assembly of MALT1 individual domains in CBM activation remains elusive. Here we report the crystal structure of the MALT1 death domain (DD) at a resolution of 2.1 Å, incorporating reconstructed residues in previously disordered loops 1 and 2. Additionally, we observe a conformational regulation element (CRE) regulating stem-helix formation in NLRPs pyrin (PYD) within the MALT1 DD structure. The structure reveals a stem-helix-mediated dimer further corroborated in solution. To elucidate how the BCL10 filament facilitates MALT1 dimerization, we reconstitute a BCL10-CARD-MALT1-DD-IG1-IG2 complex model. We propose a N+7 rule for BCL10-dependent MALT1 dimerization via the IG1-IG2 domain and for MALT1-dependent cleavage in trans. Biochemical data further indicates concentration-dependent dimerization of the MALT1 IG1-IG2 domain, facilitating MALT1 dimerization in BCL10-independent manner. Our findings provide a structural and biochemical foundation for understanding MALT1 dimeric mechanisms, shedding light on potential BCL10-independent MALT1 dimer formation and high-order BCL10-MALT1 assembly.

News (Medical) associated with BCL10

14 Apr 2022

·www.biospace.com

Exelixis Announces Initiation of First-In-Human Phase 1 Trial Evaluating XL114 Monotherapy in Patients with Non-Hodgkin’s Lymphoma

Exelixis, Inc. (Nasdaq: EXEL) today announced initiation of the dose-escalation stage of the first-in-human phase 1 trial of XL114, a novel anti-cancer compound that inhibits the CARD11-BCL10-MALT1 complex, as a monotherapy in patients with non-Hodgkin’s lymphoma (NHL) who have received prior standard therapies. The objectives of the study are to determine the recommended dose and/or the maximum tolerated dose of XL114 and to evaluate the safety and preliminary efficacy of XL114 in patients with NHL. “The initiation of the dose-escalation stage of our first-in-human phase 1 trial of XL114 marks an important milestone in our early efforts to identify treatments for people with blood cancers, such as non-Hodgkin’s lymphoma, who have exhausted known life-prolonging treatment options and are thus facing poor prognoses,” said Vicki L. Goodman, M.D., Executive Vice President, Product Development and Medical Affairs, and Chief Medical Officer, Exelixis. “Based on preclinical data demonstrating activity in lymphoma cell lines that are resistant to therapies that inhibit Bruton's tyrosine kinase, we are encouraged by the potential XL114 holds and look forward to advancing to the expansion stage once the appropriate dose is identified.” The dose-escalation stage will determine the recommended dose of XL114 in patients with advanced B- and T-cell NHL. In the cohort-expansion stage, the safety and preliminary efficacy of XL114 will be further evaluated in B-cell NHL-specific expansion cohorts, including patients with activated B-cell-like diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. The primary endpoint of the expansion stage will be objective response rate based on lymphoma-specific response criteria as assessed by the investigator. As announced last year, Exelixis in-licensed XL114 from Aurigene Discovery Technologies Limited under the companies’ July 2019 collaboration, option and license agreement. Exelixis assumed responsibility for the future clinical development, commercialization and global manufacturing of XL114.

XL-114Non-Hodgkin Lymphoma

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