Linked Life Data

16303160

Source:http://linkedlifedata.com/resource/pubmed/id/16303160

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-2-21
pubmed:abstractText
The genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains four structural genes that are homologous to genes found in other coronaviruses, and also contains six subgroup-specific open reading frames (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in apoptosis via a caspase-dependent pathway. Here, we observed that transient expression of ORF7a protein fused with myc or GFP tags at its N or C terminus inhibited cell growth and prevented BrdU incorporation in different cultural cells, suggesting that ORF7a expression may regulate cell cycle progression. Analysis by flow cytometry demonstrated that ORF7a expression was associated with blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60 h post-transfection. Similar results were observed in COS-7 and Vero cells. Mutation analysis of ORF7a revealed that the domain spanning aa 44-82 of 7a protein was essential for its cytoplasmic localization and for induction of the cell cycle arrest. After analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D3 level of mRNA transcription and expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293 cells. These results suggest that the insufficient expression of cyclin D3 may cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents cell cycle progression at G0/G1 phase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
346
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
74-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16303160-Animals, pubmed-meshheading:16303160-COS Cells, pubmed-meshheading:16303160-Cell Line, pubmed-meshheading:16303160-Cercopithecus aethiops, pubmed-meshheading:16303160-Cyclin D3, pubmed-meshheading:16303160-Cyclins, pubmed-meshheading:16303160-G0 Phase, pubmed-meshheading:16303160-G1 Phase, pubmed-meshheading:16303160-Gene Expression Regulation, pubmed-meshheading:16303160-Humans, pubmed-meshheading:16303160-Membrane Proteins, pubmed-meshheading:16303160-Mutation, pubmed-meshheading:16303160-Phosphorylation, pubmed-meshheading:16303160-RNA, Messenger, pubmed-meshheading:16303160-Retinoblastoma Protein, pubmed-meshheading:16303160-SARS Virus, pubmed-meshheading:16303160-Transcription, Genetic, pubmed-meshheading:16303160-Transfection, pubmed-meshheading:16303160-Vero Cells, pubmed-meshheading:16303160-Viral Matrix Proteins, pubmed-meshheading:16303160-Viral Proteins
pubmed:year
2006
pubmed:articleTitle
SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway.
pubmed:affiliation
Department of Pathophysiology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't