The BCL10 Knockout HAP1 Polyclonal Cells product provides a CRISPR/Cas9-edited polyclonal cell population with targeted disruption of the BCL10 gene in the HAP1 background. BCL10 encodes an essential adaptor protein that mediates NF-??B activation downstream of CARD domain-containing proteins in immune receptor signaling pathways. This polyclonal knockout pool offers a heterogeneous collection of gene-disrupted cells, enabling loss-of-function studies without clonal selection bias. The CRISPR/Cas9-mediated knockout strategy disrupts BCL10 expression, generating a versatile model for investigating BCL10-dependent signal transduction and its role in lymphocyte activation and malignancy.
HAP1 is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia (CML) cell line. Its haploid karyotype simplifies genetic manipulation and functional genomic screening, as only one allele needs to be disrupted to achieve complete gene inactivation. The HAP1 line retains key signaling modules while lacking a full lymphocyte receptor repertoire, making it a tractable system for dissecting BCL10-mediated NF-??B pathways in a clean cellular context. The near-haploid nature also facilitates unambiguous interpretation of knockout phenotypes, as it avoids complexities associated with diploid heterozygosity.
BCL10 functions as a central adaptor in the CARD11/CARMA1-BCL10-MALT1 (CBM) signalosome, where it bridges upstream CARD domain proteins, such as CARD11 and CARD9, to MALT1 paracaspase activity and IKK complex activation. Upon receptor engagement, CARD11/CARD9 recruit BCL10, which then oligomerizes and binds MALT1, promoting TRAF6 and TAK1 recruitment, ultimately leading to IKK phosphorylation. Activated IKK (IKK??/IKK??/NEMO) phosphorylates I??B??, triggering its degradation and releasing NF-??B p65/p50 for nuclear translocation. BCL10 also couples to JNK and p38 MAPK pathways, diversifying downstream transcriptional responses. As a critical node in innate and adaptive immune signaling (including TCR, BCR, and C-type lectin receptors), BCL10 integrates signals from PKC??, PKC??, and RIP2 to drive expression of cytokines, chemokines, and survival factors.
In the HAP1 background, the BCL10 knockout model provides a focused platform to study CBM-dependent NF-??B activation independently of lymphocyte-specific receptor components. The near-haploid genome eliminates gene dosage effects, enabling clean loss-of-function assessment. This system is particularly valuable for interrogating BCL10??s scaffolding role and MALT1 paracaspase activity without confounding endogenous CBM complex redundancy. Researchers can reconstitute pathway components (e.g., CARD11, MALT1) in a BCL10-null setting to map structure-function relationships and evaluate inhibitor specificity against the CBM signalosome. The model also supports synthetic lethality screens and drug?Cgene interaction studies aimed at identifying vulnerabilities in BCL10-dependent cancers.
The BCL10 Knockout HAP1 Polyclonal Cells are ideally suited for a range of functional assays, including western blotting for phospho-I??B?? and NF-??B subunits, NF-??B luciferase reporter assays, co-immunoprecipitation of CBM components, RT-qPCR of NF-??B target genes, and MALT1 activity measurements. Additional applications encompass flow cytometric analysis of surface activation markers and multiplexed cytokine secretion profiling. This knockout model enables drug target validation in MALT lymphoma and DLBCL, screening for IKK/NF-??B pathway modulators, and detailed mechanistic dissection of innate and adaptive immune receptor signaling. For further information, please contact Ascent Research.
