Linked Life Data

17413032

Source:http://linkedlifedata.com/resource/pubmed/id/17413032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-18
pubmed:abstractText
SARS-CoV 3a is a structural protein, mainly localizing to Golgi apparatus and co-localizing with SARS-CoV M in co-transfected cells. Here we observed that transient expression of 3a inhibited cell growth and prevented 5-bromodeoxyuridine incorporation, suggesting that 3a deregulated cell cycle progression. Cell cycle analysis demonstrated that 3a expression was associated with blockage of cell cycle progression at G1 phase in HEK 293, COS-7, and Vero cells 24-60 h after transfection. Mutation analysis of 3a revealed that C-terminal region (176 aa approximately 274 aa), including a potential calcium ATPase motif, was essential for induction of cell cycle arrest. Topological analysis showed that 3a predominantly located in Golgi apparatus, with its N-terminus residing in the lumen (Nlum) and C-terminus in the cytosol (Ccyt). Analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that 3a expression was correlated with a significant reduction of cyclin D3 level and phosphorylation of retinoblastoma (Rb) protein at Ser-795 and Ser-809/811, not with the expression of cyclin D1, D2, cdk4, and cdk6 in 293 cells. Increases in p53 phosphorylation on Ser-15 were observed in both SARS-CoV M and 3a transfected cells, suggesting that it might not correlate with the 3a-induced G0/G1 phase arrest. The reduction of cyclin D3 level and phosphorylation of Rb were further confirmed in SARS-CoV infected Vero cells. These results indicate that SARS-CoV 3a protein, through limiting the expression of cyclin D3, may inhibit Rb phosphorylation, which in turn leads to a block in the G1 phase of the cell cycle and an inhibition of cell proliferation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9-19
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
G1 phase cell cycle arrest induced by SARS-CoV 3a protein 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