UBXD1 is a VCP-interacting protein that is involved in ER-associated degradation.
AAA ATPase VCP and its yeast ortholog Cdc48, in a complex with the Ufd1-Npl4 heterodimer as an adaptor, play an essential role in endoplasmic reticulum-associated degradation (ERAD). Several UBX domain-containing proteins function to recruit ubiquitylated substrates to VCP/Cdc48 by binding both VCP/Cdc48 and other ERAD components such as ubiquitin ligases. Here we show that mammalian UBXD1 is an additional UBX domain-containing protein involved in the ERAD process. UBXD1 is a cytosolic protein that interacts with VCP and Derlin-1. Overexpression of UBXD1 in cells causes selective dissociation of Ufd1 from VCP, resulting in inhibition of mutant cystic fibrosis transmembrane conductance regulator (CFTR) degradation by ERAD. Additionally, depletion of endogenous UBXD1 protein by RNA interference also results in a defect in CFTR degradation. Collectively, these findings suggest that UBXD1 is a regulatory component of ERAD that may modulate the adaptor binding to VCP.
Nagahama
Masami
M
Department of Life Systems, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan. nagahama@bio.tokushima-u.ac.jp
Ohnishi
Machi
M
Kawate
Yumiko
Y
Matsui
Takayuki
T
Miyake
Hitomi
H
Yuasa
Keizo
K
Tani
Katsuko
K
Tagaya
Mitsuo
M
Tsuji
Akihiko
A
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000074405:Valosin Containing Protein
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C487709:DERL1 protein, human; D008565:Membrane Proteins; C533572:UBXN6 protein, human; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein