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Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains
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 E...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764048/ https://www.ncbi.nlm.nih.gov/pubmed/19898607 http://dx.doi.org/10.1371/journal.pone.0007604 |
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author | Kim, Ikjin Li, Yue Muniz, Paulina Rao, Hai |
author_facet | Kim, Ikjin Li, Yue Muniz, Paulina Rao, Hai |
author_sort | Kim, Ikjin |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2764048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27640482009-11-06 Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains Kim, Ikjin Li, Yue Muniz, Paulina Rao, Hai PLoS One Research Article 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. Public Library of Science 2009-10-29 /pmc/articles/PMC2764048/ /pubmed/19898607 http://dx.doi.org/10.1371/journal.pone.0007604 Text en Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Ikjin Li, Yue Muniz, Paulina Rao, Hai Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title | Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title_full | Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title_fullStr | Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title_full_unstemmed | Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title_short | Usa1 Protein Facilitates Substrate Ubiquitylation through Two Separate Domains |
title_sort | usa1 protein facilitates substrate ubiquitylation through two separate domains |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764048/ https://www.ncbi.nlm.nih.gov/pubmed/19898607 http://dx.doi.org/10.1371/journal.pone.0007604 |
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