Linked Life Data

16446359

Source:http://linkedlifedata.com/resource/pubmed/id/16446359

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-3-27
pubmed:abstractText
Ubiquitin E3 ligases are important cellular components for endoplasmic reticulum (ER)-associated degradation due to their role in substrate-specific ubiquitination, which is required for retrotranslocation (dislocation) of most unwanted proteins from the ER to the cytosol for proteasome degradation. However, our understanding of the molecular mechanisms of how E3 ligases confer substrate-specific recognition, and their role in substrate retrotranslocation is limited especially in mammalian cells. mK3 is a type III ER membrane protein encoded by murine gamma herpesvirus 68. As conferred by its N-terminal RING-CH domain, mK3 has E3 ubiquitin ligase activity. In its role as an immune evasion protein, mK3 specifically targets nascent major histocompatibility complex class I heavy chains (HC) for rapid degradation. The mechanism by which mK3 extracts HC from the ER membrane into the cytosol for proteasome-mediated degradation is unknown. Evidence is presented here that HC down-regulation by mK3 is dependent on the p97 AAA-ATPase. By contrast, the kK5 protein of Kaposi's sarcoma-associated herpesvirus is p97-independent despite the fact that it is highly homologous to mK3. mK3 protein was also found in physical association with Derlin1, an ER protein recently implicated in the retrotranslocation of HC by immune evasion protein US11, but not US2, of human cytomegalovirus. The mechanistic implications of these findings are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8636-44
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16446359-Adenosine Triphosphatases, pubmed-meshheading:16446359-Animals, pubmed-meshheading:16446359-Cell Line, pubmed-meshheading:16446359-Down-Regulation, pubmed-meshheading:16446359-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16446359-Endoplasmic Reticulum, pubmed-meshheading:16446359-Flow Cytometry, pubmed-meshheading:16446359-Fluorescent Antibody Technique, Indirect, pubmed-meshheading:16446359-Fluorescent Dyes, pubmed-meshheading:16446359-Gammaherpesvirinae, pubmed-meshheading:16446359-Histocompatibility Antigens Class I, pubmed-meshheading:16446359-Humans, pubmed-meshheading:16446359-Immunoblotting, pubmed-meshheading:16446359-L Cells (Cell Line), pubmed-meshheading:16446359-Luminescent Measurements, pubmed-meshheading:16446359-Membrane Proteins, pubmed-meshheading:16446359-Mice, pubmed-meshheading:16446359-Nuclear Proteins, pubmed-meshheading:16446359-Organic Chemicals, pubmed-meshheading:16446359-Precipitin Tests, pubmed-meshheading:16446359-Protein Structure, Tertiary, pubmed-meshheading:16446359-Retroviridae, pubmed-meshheading:16446359-Transduction, Genetic, pubmed-meshheading:16446359-Ubiquitin-Protein Ligases, pubmed-meshheading:16446359-Ubiquitins
pubmed:year
2006
pubmed:articleTitle
The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins.
pubmed:affiliation
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural