The BAP1 Knockout TE1 Polyclonal Cells product consists of a CRISPR/Cas9-edited polyclonal population of TE1 human esophageal squamous cell carcinoma (ESCC) cells with targeted disruption of the BAP1 gene. As a polyclonal knockout pool, this product provides a heterogeneous mixture of loss-of-function genotypes, enabling robust modeling of BAP1 deficiency without the limitations of clonal selection. This format is generated by Cas9-mediated DNA cleavage and subsequent repair via non-homologous end joining, resulting in diverse mutations that broadly ablate BAP1 protein expression.
The TE1 host cell line is a well-established model of human ESCC, derived from a primary tumor and characterized by a mutant TP53 background. TE1 cells recapitulate key features of esophageal cancer, including genomic instability, aberrant proliferation, and resistance to apoptosis. Integrating BAP1 knockout into this p53-deficient context creates a clinically relevant system for investigating the cooperative effects of dual tumor suppressor loss, which frequently co-occurs in esophageal malignancies.
BAP1 functions as a deubiquitinase that removes monoubiquitin from histone H2A at Lys119, antagonizing polycomb-group-mediated transcriptional repression. It operates within the PR-DUB complex, interacting with ASXL1/2, FOXK1/2, HCFC1, and chromatin modifiers such as OGT, KDM1B, and MBD5/6. Upon DNA damage, ATM-phosphorylated BAP1 accumulates at damage sites, associating with BRCA1, BARD1, and ??H2AX to facilitate homologous recombination repair. BAP1 also stabilizes HCFC1 and regulates the INK4a/ARF locus and p53 target genes, thereby coordinating DNA repair, cell cycle arrest, and apoptosis. Consequently, BAP1 disruption compromises these tumor-suppressive pathways, enhancing genomic instability and prosurvival signaling.
In the TP53-mutant TE1 background, BAP1 knockout further impairs DNA damage responses and apoptotic programs, potentially accelerating malignant phenotypes typical of advanced ESCC. This model serves as a powerful tool to dissect how BAP1 loss cooperates with p53 dysfunction to drive tumor aggressiveness, therapeutic resistance, and chromosomal instability. It enables the identification of synthetic lethal dependencies and the characterization of BAP1??s role in maintaining epithelial differentiation and chromatin homeostasis in esophageal cancer.
Key applications include mechanistic studies of tumor suppression, DNA damage signaling, and chromatin regulation, as well as drug sensitivity profiling with agents such as cisplatin and PARP inhibitors. Standard assays include Western blotting for BAP1 and downstream targets (e.g., H2AK119ub, HCFC1), RT-qPCR for BAP1 target genes, ChIP for histone modifications, immunofluorescence for ??H2AX foci, and flow cytometry for cell cycle and apoptosis. This polyclonal knockout population is also suitable for pooled CRISPR screens and in vivo xenograft models. For additional information, please contact Ascent Research.
