TY - JOUR
T1 - Usa1 protein facilitates substrate ubiquitylation through two separate domains
AU - Kim, Ikjin
AU - Li, Yue
AU - Muniz, Paulina
AU - Rao, Hai
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/10/29
Y1 - 2009/10/29
N2 - Background: Defects in protein folding are recognized as the root of many neurodegenerative disorders. In the endoplasmic reticulum (ER), secretory proteins are subjected to a stringent quality control process to eliminate misfolded proteins by the ER-associated degradation (ERAD) pathway. A novel ERAD component Usa1 was recently identified. However, the specific role of Usa1 in ERAD remains obscure. Methodology/Principal Findings: Here, we demonstrate that Usa1 is important for substrate ubiquitylation. Furthermore, we defined key cis-elements of Usa1 essential for its degradation function. Interestingly, a putative proteasome-binding motif is dispensable for the functioning of Usa1 in ERAD. We identify two separate cytosolic domains critical for Usa1 activity in ERAD, one of which is involved in binding to the Ub-protein ligase Hrd1/Hrd3. Usa1 may have another novel role in substrate ubiquitylation that is separate from the Hrd1 association. Conclusions/Significance: We conclude that Usa1 has two important roles in ERAD substrate ubiquitylation.
AB - Background: Defects in protein folding are recognized as the root of many neurodegenerative disorders. In the endoplasmic reticulum (ER), secretory proteins are subjected to a stringent quality control process to eliminate misfolded proteins by the ER-associated degradation (ERAD) pathway. A novel ERAD component Usa1 was recently identified. However, the specific role of Usa1 in ERAD remains obscure. Methodology/Principal Findings: Here, we demonstrate that Usa1 is important for substrate ubiquitylation. Furthermore, we defined key cis-elements of Usa1 essential for its degradation function. Interestingly, a putative proteasome-binding motif is dispensable for the functioning of Usa1 in ERAD. We identify two separate cytosolic domains critical for Usa1 activity in ERAD, one of which is involved in binding to the Ub-protein ligase Hrd1/Hrd3. Usa1 may have another novel role in substrate ubiquitylation that is separate from the Hrd1 association. Conclusions/Significance: We conclude that Usa1 has two important roles in ERAD substrate ubiquitylation.
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U2 - 10.1371/journal.pone.0007604
DO - 10.1371/journal.pone.0007604
M3 - Article
C2 - 19898607
AN - SCOPUS:70449558838
VL - 4
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e7604
ER -