Linked Life Data

15096051

Source:http://linkedlifedata.com/resource/pubmed/id/15096051

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2004-4-20
pubmed:abstractText
Co- and posttranslational regulation of apolipoprotein B (apoB) has been postulated to involve degradation by both proteasomal and nonproteasomal pathways; however, nonproteasomal mechanisms of apoB degradation are currently unknown. We have previously demonstrated an intracellular association of newly synthesized apoB with endoplasmic reticulum (ER)-60, an ER-localized protein, possessing both proteolytic and chaperone activities. In the present paper, adenoviral expression vectors containing rat ER-60 cDNA were used to achieve dose- and time-dependent overexpression of ER-60 to investigate its role in apoB100 turnover. Overexpressed ER-60 accumulated in the microsomal lumen of HepG2 cells and was associated with apoB100 in dense lipoprotein particles. Overexpression of ER-60 in HepG2 cells significantly reduced both intracellular and secreted apoB100, with no effect on the secretion of a control protein, albumin. Similar results were obtained in McA-RH7777 rat hepatoma cells. ER-60-stimulated apoB100 degradation and inhibition of apoB100 secretion were sensitive to the protease inhibitor, p-chloromercuribenzoate (pCMB), in a dose-dependent manner but were unaffected by the proteasomal or lysosomal protease inhibitors, N-acetyl-leucinyl-leucinyl-nor-leucinal, E64, and leupeptin. Interestingly, enhanced expression of ER-60 induced apoB100 fragmentation in permeabilized HepG2 cells and resulted in detection of a unique 50 kDa degradation intermediate, a process that could be inhibited by pCMB. Intracellular stability and secretion of apoB100 in primary hamster hepatocytes were also found to be sensitive to pCMB. When taken together, the data suggest an important role for ER-60 in promoting apoB100 degradation via a pCMB-sensitive process in the ER. ER-60 may act directly as a protease or may be involved indirectly as a chaperone/protein factor targeting apoB100 to this nonproteasomal and pCMB-sensitive degradative pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4819-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15096051-Adenoviridae, pubmed-meshheading:15096051-Animals, pubmed-meshheading:15096051-Apolipoprotein B-100, pubmed-meshheading:15096051-Apolipoproteins B, pubmed-meshheading:15096051-Cell Line, pubmed-meshheading:15096051-Cell Line, Tumor, pubmed-meshheading:15096051-Cell Membrane Permeability, pubmed-meshheading:15096051-Chloromercuribenzoates, pubmed-meshheading:15096051-Cricetinae, pubmed-meshheading:15096051-Cysteine Endopeptidases, pubmed-meshheading:15096051-Cysteine Proteinase Inhibitors, pubmed-meshheading:15096051-Down-Regulation, pubmed-meshheading:15096051-Endoplasmic Reticulum, pubmed-meshheading:15096051-Genetic Vectors, pubmed-meshheading:15096051-Hepatocytes, pubmed-meshheading:15096051-Humans, pubmed-meshheading:15096051-Intracellular Fluid, pubmed-meshheading:15096051-Microsomes, pubmed-meshheading:15096051-Rats, pubmed-meshheading:15096051-Signal Transduction, pubmed-meshheading:15096051-Transduction, Genetic
pubmed:year
2004
pubmed:articleTitle
Overexpression of the endoplasmic reticulum 60 protein ER-60 downregulates apoB100 secretion by inducing its intracellular degradation via a nonproteasomal pathway: evidence for an ER-60-mediated and pCMB-sensitive intracellular degradative pathway.
pubmed:affiliation
Division of Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada M5G 1X8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't