Lee, Jae-Jin Park, Joon Kyu Jeong, Jaeho Jeon, Hyesung Yoon, Jong-Bok Kim, Eunice EunKyeong Lee, Kong-Joo 2024-01-20T12:34:32Z 2024-01-20T12:34:32Z 2021-09-01 2013-03-08 0021-9258 https://pubs.kist.re.kr/handle/201004/128250 Fas-associated factor 1 (FAF1) is a ubiquitin receptor containing multiple ubiquitin-related domains including ubiquitin-associated (UBA), ubiquitin-like (UBL) 1, UBL2, and ubiquitin regulatory X (UBX). We previously showed that N-terminal UBA domain recognizes Lys(48)-ubiquitin linkage to recruit polyubiquitinated proteins and that a C-terminal UBX domain interacts with valosin-containing protein (VCP). This study shows that FAF1 interacts only with VCP complexed with Npl4-Ufd1 heterodimer, a requirement for the recruitment of polyubiquitinated proteins to UBA domain. Intriguingly, VCP association to C-terminal UBX domain regulates ubiquitin binding to N-terminal UBA domain without direct interaction between UBA and UBX domains. These interactions are well characterized by structural and biochemical analysis. VCP-Npl4-Ufd1 complex is known as the machinery required for endoplasmic reticulum-associated degradation. We demonstrate here that FAF1 binds to VCP-Npl4-Ufd1 complex via UBX domain and polyubiquitinated proteins via UBA domain to promote endoplasmic reticulum-associated degradation. English AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC AAA ATPASE P97/VCP POSTTRANSLATIONAL MODIFICATIONS UBIQUITIN LIGASES UBX DOMAIN BINDING IDENTIFICATION CDC48/P97 COFACTORS INTERACTS STRATEGY Complex of Fas-associated Factor 1 (FAF1) with Valosin-containing Protein (VCP)-Npl4-Ufd1 and Polyubiquitinated Proteins Promotes Endoplasmic Reticulum-associated Degradation (ERAD) Article 10.1074/jbc.M112.417576 1 JOURNAL OF BIOLOGICAL CHEMISTRY, v.288, no.10, pp.6998 - 7011 JOURNAL OF BIOLOGICAL CHEMISTRY 288 10 6998 7011 scie scopus 000316002400022 2-s2.0-84874871591 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article AAA ATPASE P97/VCP POSTTRANSLATIONAL MODIFICATIONS UBIQUITIN LIGASES UBX DOMAIN BINDING IDENTIFICATION CDC48/P97 COFACTORS INTERACTS STRATEGY