{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Grothusen GP"],"funding":["American Cancer Society","NHLBI NIH HHS","American Cancer Society (American Cancer Society, Inc.)","Center for Strategic Scientific Initiatives, National Cancer Institute (NCI Center for Strategic Scientific Initiatives)","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","NCI NIH HHS","Center for Strategic Scientific Initiatives, National Cancer Institute","U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)","NIGMS NIH HHS"],"pagination":["5604"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11222469"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency. Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes co"],"journal":["Nature communications"],"pubmed_title":["DCAF15 control of cohesin dynamics sustains acute myeloid leukemia."],"pmcid":["PMC11222469"],"funding_grant_id":["R01 CA207513","R01HL159175","R01 CA258904","P30 CA010815","R01 GM143229","R01 GM101149","R01-CA258904","RSG-19-199-01","R01 HL159175","R50 CA221838","R01 CA174904"],"pubmed_authors":["Grothusen GP","Zhou N","Datta A","Chang R","Wang B","Tang HY","Wulfridge P","Sarma K","Busino L","Zheng N","Cao Z","Beer T","Shi J","Greenberg RA","Mittal M"],"additional_accession":[]},"is_claimable":false,"name":"DCAF15 control of cohesin dynamics sustains acute myeloid leukemia.","description":"The CRL4-DCAF15 E3 ubiquitin ligase complex is targeted by the aryl-sulfonamide molecular glues, leading to neo-substrate recruitment, ubiquitination, and proteasomal degradation. However, the physiological function of DCAF15 remains unknown. Using a domain-focused genetic screening approach, we reveal DCAF15 as an acute myeloid leukemia (AML)-biased dependency. Loss of DCAF15 results in suppression of AML through compromised replication fork integrity and consequent accumulation of DNA damage. Accordingly, DCAF15 loss sensitizes AML to replication stress-inducing therapeutics. Mechanistically, we discover that DCAF15 directly interacts with the SMC1A protein of the cohesin complex and destabilizes the cohesin regulatory factors PDS5A and CDCA5. Loss of PDS5A and CDCA5 removal precludes co","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-05-29T09:39:45.644Z","creation":"2025-04-21T16:12:33.229Z"},"accession":"S-EPMC11222469","cross_references":{"pubmed":["38961054"],"doi":["10.1038/s41467-024-49882-x"]}}