Kim, Yeon Jung Das, Tanuza Park, Jinyoung Hwang, Inah Kim, Eunice EunKyeong Song, Eun Joo 2025-11-17T01:42:04Z 2025-11-17T01:42:04Z 2025-11-11 2026-03 1350-9047 https://pubs.kist.re.kr/handle/201004/153492 Ubiquitin removal by deubiquitinating enzymes (DUBs) is a crucial cellular process. Among the DUBs, ubiquitin-specific protease 13 (USP13) is overexpressed in multiple cancers and is associated with tumorigenesis and poor prognosis. However, its involvement in the cell death pathway is poorly understood. Thus, we describe the novel function of USP13 as a crucial regulator of necroptosis. USP13 interacts with cellular IAP2 (cIAP2), stabilizing cIAP2 proteins in colorectal cancer (CRC) cells. The TCGA-COAD and GEO databases revealed USP13 upregulation in CRC patients and its association with poor clinical outcomes. The loss of USP13 significantly potentiates TNF-α/SMAC mimetic birinapant/pan-caspase inhibitor Z-VAD-FMK (TBZ)–induced necroptosis in CRC cells and diminishes tumor growth in a xenograft model. Thereby, USP13 may serve as a potential therapeutic target for anticancer treatment of CRC. English Nature Publishing Group USP13 depletion sensitizes colorectal cancer cells to necroptosis by destabilizing cIAP2 proteins Article 10.1038/s41418-025-01595-4 1 Cell Death & Differentiation, v.33, pp.643 - 655 Cell Death & Differentiation 33 643 655 N scie scopus 2-s2.0-105019625754 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article; Early Access SMAC DEUBIQUITYLATION UBIQUITINATION STABILIZATION INHIBITION INDUCTION STABILITY KINASE PTEN NF-KAPPA-B