Le, Ly Thi Huong Luu Park, Seoyoung Lee, Jung Hoon Kim, Yun Kyung Lee, Min Jae 2024-07-18T07:30:33Z 2024-07-18T07:30:33Z 2024-07-18 2024-01 1016-8478 https://pubs.kist.re.kr/handle/201004/150273 In eukaryotes, a primary protein quality control (PQC) process involves the destruction of conformationally misfolded proteins through the ubiquitin-proteasome system. Because approximately one-third of eukaryotic proteomes fold and assemble within the endoplasmic reticulum (ER) before being sent to their destinations, the ER plays a crucial role in PQC. The specific functions and biochemical roles of several E3 ubiquitin ligases involved in ER -associated degradation in mammals, on the other hand, are mainly unknown. We identified 2 E3 ligases, ubiquitin protein ligase E3 component Nrecognin 1 (UBR1) and ubiquitin protein ligase E3 component N-recognin 2 (UBR2), which are the key N-recognins in the Ndegron pathway and participate in the ER stress response in mammalian cells by modulating their stability. Cells lacking UBR1 and UBR2 are hypersensitive to ER stress -induced apoptosis. Under normal circumstances, these proteins are polyubiquitinated through Lys48-specific linkages and are then degraded by the 26S proteasome. In contrast, when cells are subjected to ER stress, UBR1 and UBR2 exhibit greater stability, potentially as a cellular adaptive response to stressful conditions. Although the precise mechanisms underlying these findings require further investigation, our findings show that cytoplasmic UBR1 and UBR2 have anti -ER stress activities and contribute to global PQC in mammals. These data also reveal an additional level of complexity within the mammalian ER -associated degradation system, implicating potential involvement of the N-degron pathway. English 한국분자세포생물학회 N-recognins UBR1 and UBR2 as central ER stress sensors in mammals Article 10.1016/j.mocell.2023.12.001 1 Molecules and Cells, v.47, no.1, pp.1 - 8 Molecules and Cells 47 1 1 8 Y scie scopus kci ART003104837 001261995300001 2-s2.0-85185704460 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article END RULE PATHWAY PROTEIN-QUALITY CONTROL UBIQUITIN LIGASES UBR1 ARGINYLATION DEGRADATION COMPONENTS Auto-ubiquitination Endoplasmic reticulum stress N-degron pathway Protein quality control Thapsigargin