Linked Life Data

14972545

Source:http://linkedlifedata.com/resource/pubmed/id/14972545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-2-19
pubmed:abstractText
The nonstructural protein 2C is highly conserved among picornaviruses and plays an important role in the assembly of mature virions, membrane association, and viral RNA synthesis. The investigation of other potential functions of nonstructural protein 2C from avian encephalomyelitis virus (AEV) resulted in identifying for the first time that the protein 2C is involved in apoptosis. Expression of the protein 2C on chick embryo brain (CEB) and Cos-7 cells produced TUNEL-positive cells characterized by a cleavage of cellular DNA and the formation of membrane-enclosed apoptotic bodies. Analysis of the protein 2C showed that the N-terminal domain containing 35 amino acid (aa) residues (between 46 and 80 aa) is associated with apoptotic function. Transfection of the deletion mutant lacking this 35 aa's into CEB and Cos-7 cells failed to induce apoptosis. Furthermore, the protein 2C induced apoptosis in the transfected CEB and Cos-7 cells through activation of caspase-9 rather than caspase-8 followed by activation of caspase-3 pathway. Analysis of the Western blots of caspase-3 and caspase-9 showed the characteristics of active caspase-3 and -9 in the 2C-transfected CEB and Cos-7 cells as seen in the AEV-infected CEB cells while they were in the form of procaspase-3 and procaspase-9 in the 2C mutant-transfected cells. To further elucidate the mechanism of the 2C-induced apoptosis, the 2C-transfected CEB and Cos-7 cells were fractionated into mitochondria and cytosol and subjected for Western blotting, located cytochrome c in the mitochondria as well as the cytosol fractions, while it was only sequestered in the mitochondrial fraction in the mutant 2C-transfected cells. The protein 2C was located in the mitochondria and cytosol of the transfected/infected CEB and transfected Cos-7 cells, but the mutant lost its ability to localize to the mitochondria. Altogether, the results demonstrate that the protein 2C localized to the mitochondria of the transfected cells triggered the efflux of cytochrome c into the cytosol in turn activating the upstream caspase-9 and then the downstream caspase-3, thus leading to apoptosis in the cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
318
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
169-82
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Avian encephalomyelitis virus nonstructural protein 2C induces apoptosis by activating cytochrome c/caspase-9 pathway.
pubmed:affiliation
Animal Health Biotechnology Unit, Temasek Life Sciences Laboratory, The National University of Singapore, 117604 Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't