The BAG5 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human renal cell adenocarcinoma line. This product disrupts the BAG5 gene, encoding a co-chaperone that regulates protein homeostasis and cell survival. The polyclonal format provides a heterogeneous edited cell pool, enabling robust functional studies while minimizing clonal artifacts.
786-O is a tumorigenic renal epithelial line from a primary clear cell renal cell carcinoma (ccRCC) of a 58-year-old male. It harbors a VHL truncating mutation and expresses wild-type PTEN. Loss of VHL stabilizes HIF1A, driving a pseudohypoxic program that promotes survival, angiogenesis, and metabolic adaptation, making it a key model for ccRCC and stress biology.
BAG5 acts as a nucleotide exchange factor for HSP70, modulating the HSP70/HSP90 chaperone cycle. It inhibits the E3 ligase parkin, suppressing mitophagy, and stabilizes anti-apoptotic Bcl-2 proteins. BAG5 interacts with HSP70, HSP90, parkin, Bcl-2, CHIP, and HSC70. Upstream regulators include cellular stress, heat shock, androgen signaling, and HIF1A; downstream targets involve HSP70, parkin, Bcl-2, androgen receptor, LC3, and p62, linking BAG5 to autophagy and apoptosis control.
In VHL-mutant 786-O cells, constitutive HIF1A activation may heighten dependence on BAG5-mediated chaperone assistance. Knocking out BAG5 is expected to impair HSP70-dependent protein folding, derepress parkin-mediated mitophagy, and promote apoptosis, thereby reducing tumor cell fitness. This model enables dissection of co-chaperone roles in sustaining ccRCC survival under proteotoxic stress.
Applications include probing BAG5-dependent mechanisms in ccRCC, autophagy modulation, apoptosis regulation, and drug resistance. Assays such as Western blotting for BAG5, HSP70, Bcl-2, LC3; co-immunoprecipitation of BAG5 with HSP70/parkin; Annexin V/PI apoptosis detection; MTT/CCK-8 viability; immunofluorescence for autophagy markers; RT-qPCR; and migration/invasion assays are facilitated. This knockout model supports studies of the HSP70 chaperone network, parkin activator screening, and stress survival pathway analysis. For further information, contact Ascent Research.
