The DTD1 Knockout 786-O Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal population of 786-O human renal cell carcinoma cells carrying a disruption in the DTD1 gene. This product provides a heterogeneous pool of edited cells suitable for studying the loss-of-function effects of DTD1 in a clear cell renal cell carcinoma (ccRCC) background. The polyclonal format avoids clonal selection artifacts while enabling robust analysis of DTD1-dependent phenotypes.
The parental 786-O cell line was established from a primary clear cell adenocarcinoma of the kidney and is a widely used model of VHL-mutant ccRCC. These cells harbor a mutated von Hippel-Lindau (VHL) tumor suppressor gene, leading to constitutive activation of hypoxia-inducible factor (HIF) signaling, a hallmark of ccRCC. The 786-O background thus provides a disease-relevant context for investigating molecular mechanisms underlying kidney cancer.
DTD1 (D-tyrosyl-tRNA deacylase 1) hydrolyzes D-aminoacyl-tRNAs to prevent incorporation of D-amino acids into nascent polypeptides, thereby maintaining translational fidelity. Upstream regulators such as E2F1 and MYC, along with growth factor signaling, control DTD1 expression. Loss of DTD1 function leads to accumulation of D-aminoacyl-tRNAs, resulting in proteotoxic stress and activation of the unfolded protein response (UPR). This triggers downstream effectors including ATF4 and CHOP, which promote cell cycle arrest through p21-mediated inhibition of CDK2/cyclin E complexes. DTD1 interacts with D-aminoacyl-tRNAs and aminoacyl-tRNA synthetases at the ribosome, positioning it as a critical guardian of proteome integrity.
In the 786-O ccRCC model, disruption of DTD1 generates a physiologically relevant system to explore the interplay between translational control and tumor suppression. The VHL-mutant background, characterized by aberrant protein synthesis and metabolic stress, sensitizes these cells to perturbations in translation fidelity. DTD1 knockout is expected to induce D-amino acid misincorporation, leading to protein aggregation, UPR activation, and growth inhibition, recapitulating key aspects of the mechanistic summary. This model enables dissection of how proteotoxic stress interfaces with oncogenic signaling in renal cancer, and provides a platform for evaluating DTD1 as a potential therapeutic target.
Researchers can employ this polyclonal knockout product in a variety of assays, including Western blotting and RT-qPCR to assess downstream target expression (e.g., ATF4, CHOP, p21), proliferation and clonogenic survival assays to measure growth effects, and flow cytometry for cell cycle and apoptosis analysis. Puromycin incorporation assays can directly probe translation rates, while tumor xenograft studies in mice may evaluate in vivo tumorigenicity. Functional genomics screens in the DTD1-null background can identify synthetic lethal interactions and novel regulators of translation quality control in ccRCC. For further information, please contact Ascent Research.
