Linked Life Data

16987818

Source:http://linkedlifedata.com/resource/pubmed/id/16987818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2006-11-13
pubmed:abstractText
Improperly folded proteins in the endoplasmic reticulum (ER) are eliminated via ER-associated degradation, a process that dislocates misfolded proteins from the ER membrane into the cytosol, where they undergo proteasomal degradation. Dislocation requires a subclass of ubiquitin ligases that includes gp78 in addition to the AAA ATPase p97/VCP and its cofactor, the Ufd1-Npl4 dimer. We have previously reported that gp78 interacts directly with p97/VCP. Here, we identify a novel p97/VCP-interacting motif (VIM) within gp78 that mediates this interaction. We demonstrate that the VIM of gp78 recruits p97/VCP to the ER, but has no effect on Ufd1 localization. We also show that gp78 VIM interacts with the ND1 domain of p97/VCP that was shown previously to be the binding site for Ufd1. To evaluate the role of Ufd1 in gp78-p97/VCP-mediated degradation of CD3delta, a known substrate of gp78, RNA interference was used to silence the expression of Ufd1 and p97/VCP. Inhibition of p97/VCP, but not Ufd1, stabilized CD3delta in cells that overexpress gp78. However, both p97/VCP and Ufd1 appear to be required for CD3delta degradation in cells expressing physiological levels of gp78. These results raise the possibility that Ufd1 and gp78 may bind p97/VCP in a mutually exclusive manner and suggest that gp78 might act in a Ufd1-independent degradation pathway for misfolded ER proteins, which operates in parallel with the previously established p97/VCP-Ufd1-Npl4-mediated mechanism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AMFR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Amfr protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3, http://linkedlifedata.com/resource/pubmed/chemical/CD3delta antigen, http://linkedlifedata.com/resource/pubmed/chemical/CDC48 protein, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, 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/Ubiquitin-Protein Ligases, http://linkedlifedata.com/resource/pubmed/chemical/Ufd1l protein, mouse
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35359-68
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation.
pubmed:affiliation
Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural