Complex of FAF1 with VCP-Npl4-Ufd1 and polyubiquitinated proteins promotes endoplasmic reticulum-associated degradation (ERAD).

Fas-associated factor 1 (FAF1) is an ubiquitin receptor containing multiple ubiquitin related domains including UBA, UBL1, UBL2, and UBX. We previously showed that N-terminal UBA domain recognizes K48-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 domain. 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 (ERAD). We demonstrate here that FAF1 binds to VCP-Npl4-Ufd1 complex via UBX domain and polyubiquitinated proteins via UBA domain to promote ERAD. to promote ERAD.
J. Biol. Chem.
Date: Jan. 04, 2013
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