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rdf:type |
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lifeskim:mentions |
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0063164,
umls-concept:C0178555,
umls-concept:C0205360,
umls-concept:C0600138,
umls-concept:C1156530,
umls-concept:C1332083,
umls-concept:C1421316,
umls-concept:C1554080,
umls-concept:C1706198,
umls-concept:C1998811
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pubmed:issue |
2
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pubmed:dateCreated |
2007-8-7
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pubmed:abstractText |
The membrane-anchored ubiquitin ligase gp78 promotes degradation of misfolded endoplasmic reticulum (ER) proteins and sterol-regulated degradation of HMG-CoA reductase. It was known previously that Ufd1 plays a critical role in ER-associated degradation (ERAD) together with Npl4 and VCP. The VCP-Ufd1-Npl4 complex recognizes polyubiquitin chains and transfers the ubiquitinated proteins to the proteasome. Here we show that Ufd1 directly interacts with gp78 and functions as a cofactor. Ufd1 enhances the E3 activity of gp78, accelerates the ubiquitination and degradation of reductase, and eventually promotes receptor-mediated uptake of low-density lipoprotein. Furthermore, we demonstrate that the monoubiquitin-binding site in Ufd1 is required for the enhancement of gp78 activity and that the polyubiquitin-binding site in Ufd1 is critical for a postubiquitination step in ERAD. In summary, our study identifies Ufd1 as a cofactor of gp78, reveals an unappreciated function of Ufd1 in the ubiquitination reaction during ERAD, and illustrates that Ufd1 plays a critical role in cholesterol metabolism.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AMFR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl CoA Reductases,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Autocrine Motility Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine,
http://linkedlifedata.com/resource/pubmed/chemical/UFD1L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1550-4131
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
115-28
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17681147-Amino Acids,
pubmed-meshheading:17681147-Animals,
pubmed-meshheading:17681147-Binding Sites,
pubmed-meshheading:17681147-CHO Cells,
pubmed-meshheading:17681147-Cell Line,
pubmed-meshheading:17681147-Cholesterol,
pubmed-meshheading:17681147-Cricetinae,
pubmed-meshheading:17681147-Cricetulus,
pubmed-meshheading:17681147-Enzyme Stability,
pubmed-meshheading:17681147-Humans,
pubmed-meshheading:17681147-Hydroxymethylglutaryl CoA Reductases,
pubmed-meshheading:17681147-Lipoproteins, LDL,
pubmed-meshheading:17681147-Models, Biological,
pubmed-meshheading:17681147-Protein Binding,
pubmed-meshheading:17681147-Protein Interaction Mapping,
pubmed-meshheading:17681147-Protein Processing, Post-Translational,
pubmed-meshheading:17681147-Protein Structure, Tertiary,
pubmed-meshheading:17681147-Proteins,
pubmed-meshheading:17681147-Receptors, Autocrine Motility Factor,
pubmed-meshheading:17681147-Receptors, Cytokine,
pubmed-meshheading:17681147-Ubiquitin,
pubmed-meshheading:17681147-Ubiquitin-Protein Ligases
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pubmed:year |
2007
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pubmed:articleTitle |
Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase.
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pubmed:affiliation |
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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