Linked Life Data

12533700

Source:http://linkedlifedata.com/resource/pubmed/id/12533700

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 1
pubmed:dateCreated
2003-1-20
pubmed:abstractText
In human cytomegalovirus (HCMV) infection, the isolated expression of the viral immediate-early protein 2 (IE2) 86 kDa regulatory protein coincides with an up-regulation of cyclin E gene expression, both in fibroblasts and U373 cells. Since IE2 also interferes with cell-cycle progression, it is unclear whether IE2 is a genuine activator of cyclin E or whether IE2-arrested cells contain elevated levels of cyclin E primarily as a consequence of them being arrested at the beginning of S phase. It is important to distinguish between these possibilities in order to define and analyse at a mechanistic level the proliferative and anti-proliferative capacities of IE2. Here we have shown that IE2 can activate cyclin E independent of the cell-cycle state and can therefore function as a genuine activator of cyclin E gene expression. A mutant of IE2 that failed to activate cyclin E also failed to promote G1/S transition. Instead, cells became arrested in G1. S-phase entry could be rescued in these cells by co-expression of cyclin E, but these cells still arrested in early S phase, as is the case with wild-type IE2. Our data demonstrate that IE2 can promote two independent cell-cycle functions at the same time: (i) the induction of G1/S transition via up-regulation of cyclin E, and (ii) a block in cell-cycle progression in early S phase. In G1, the proliferative activity of IE2 appears to be dominant over the anti-proliferative force, whereas after G1/S transition, this situation is reversed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Human cytomegalovirus immediate-early protein 2 (IE2)-mediated activation of cyclin E is cell-cycle-independent and forces S-phase entry in IE2-arrested cells.
pubmed:affiliation
Department of Pediatrics, Laboratory for Molecular Biology, Charité, CCM-Ziegelstr. 5-9, Humboldt-University, Berlin, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't