biostudies-literatureUnknown31(2)La Marca JEWhole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a Cell death and differentiation150-158https://www.ebi.ac.uk/biostudies/studies/S-EPMC10850147biostudies-literatureGenome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.PMC10850147Milla LWilcox SKelly GLTai LDiepstraten STYang BAubrey BJStrasser AHerold MJLa Marca JEHeinzel SVremec DKueh AWhelan LKonig CKaloni DVoss AKChang CWang ZfalseGenome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a 2024-01-01T00:00:00Z2024 Feb2025-04-04T10:42:01.813Z2025-04-04T10:42:01.813ZS-EPMC108501473809762210.1038/s41418-023-01249-3