biostudies-literatureUnknown21(5)Liu Jthe Swedish Cancer FoundationSwedish Research Councilthe Karolinska InstitutetThe synthesis of membrane and secreted proteins is safeguarded by an endoplasmic reticulum-associated ribosome quality control (ER-RQC) that promotes the disposal of defective translation products by the proteasome or via a lysosome-dependent pathway involving the degradation of portions of the ER by macroautophagy (reticulophagy). The UFMylation of RPL26 on ER-stalled ribosomes is essential for activating the ER-RQC and reticulophagy. Here, we report that the viral deubiquitinase (vDUB) encoded in the N-terminal domain of the Epstein-Barr virus (EBV) large tegument protein BPLF1 hinders the UFMylation of RPL26 on ribosomes that stall at the ER, promotes the stabilization of ER-RQC substrates, and inhibits reticulophagy. The vDUB did not act as a de-UFMylase or interfere with the UFMylatioAutophagy996-1018https://www.ebi.ac.uk/biostudies/studies/S-EPMC12013442biostudies-literatureThe Epstein-Barr virus deubiquitinase BPLF1 regulates stress-induced ribosome UFMylation and reticulophagy.PMC12013442Bleuse SLiu JNagy NAyala-Torres CLarsson OAguilar-Alonso FMasucci MGfalseThe Epstein-Barr virus deubiquitinase BPLF1 regulates stress-induced ribosome UFMylation and reticulophagy.The synthesis of membrane and secreted proteins is safeguarded by an endoplasmic reticulum-associated ribosome quality control (ER-RQC) that promotes the disposal of defective translation products by the proteasome or via a lysosome-dependent pathway involving the degradation of portions of the ER by macroautophagy (reticulophagy). The UFMylation of RPL26 on ER-stalled ribosomes is essential for activating the ER-RQC and reticulophagy. Here, we report that the viral deubiquitinase (vDUB) encoded in the N-terminal domain of the Epstein-Barr virus (EBV) large tegument protein BPLF1 hinders the UFMylation of RPL26 on ribosomes that stall at the ER, promotes the stabilization of ER-RQC substrates, and inhibits reticulophagy. The vDUB did not act as a de-UFMylase or interfere with the UFMylatio2025-01-01T00:00:00Z2025 May2026-07-15T11:03:23.58Z2025-07-07T03:10:05.705ZS-EPMC120134423984245410.1080/15548627.2024.2440846