Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 288, Issue 10, Pages 6998-7011Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.417576
Keywords
-
Categories
Funding
- Center for Cell Signaling Research and Drug Discovery Research Grant at Ewha Womans University from the National Core Research Center program, [R15-2006-020]
- Global Research Laboratory Program [2012045441]
- Bio and Medical Technology Development Program of the National Research Foundation of Korea [2012035580]
- Functional Proteomics Center
- Korea Ministry of Science and Technology, and an institutional grant from the Korea Institute of Science and Technology
- Korea Institute of Science and Technology
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available