| pubmed-article:18588506 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0596290 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0079183 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0449258 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0288590 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C2587213 | lld:lifeskim |
| pubmed-article:18588506 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:18588506 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:18588506 | pubmed:dateCreated | 2008-10-9 | lld:pubmed |
| pubmed-article:18588506 | pubmed:abstractText | In the present study, we examined the role of PLC delta 1 (phospholipase C delta 1) in the regulation of cellular proliferation. We demonstrate that RNAi (RNA interference)-mediated knockdown of endogenous PLC delta 1, but not PLC beta 3 or PLC epsilon, induces a proliferation defect in Rat-1 and NIH 3T3 fibroblasts. The decreased proliferation was not due to an induction of apoptosis or senescence, but was associated with an approx. 60% inhibition of [(3)H]thymidine incorporation. Analysis of the cell cycle with BrdU (bromodeoxyuridine)/propidium iodide-labelled FACS (fluorescence-activated cell sorting) demonstrated an accumulation of cells in G(0)/G(1)-phase and a corresponding decrease in cells in S-phase. Further examination of the cell cycle after synchronization by serum-starvation demonstrated normal movement through G(1)-phase but delayed entry into S-phase. Consistent with these findings, G(1) cyclin (D2 and D3) and CDK4 (cyclin-dependent kinase 4) levels and associated kinase activity were not affected. However, cyclin E-associated CDK2 activity, responsible for G(1)-to-S-phase progression, was inhibited. This decreased activity was accompanied by unchanged CDK2 protein levels and paradoxically elevated cyclin E and cyclin E-associated CDK2 levels, suggesting inhibition of the cyclin E-CDK2 complex. This inhibition was not due to altered stimulatory or inhibitory phosphorylation of CDK2. However, p27, a Cip/Kip family CKI (CDK inhibitor)-binding partner, was elevated and showed increased association with CDK2 in PLC delta 1-knockdown cells. The result of the present study demonstrate a novel and critical role for PLC delta 1 in cell-cycle progression from G(1)-to-S-phase through regulation of cyclin E-CDK2 activity and p27 levels. | lld:pubmed |
| pubmed-article:18588506 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18588506 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18588506 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18588506 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18588506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18588506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18588506 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18588506 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18588506 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:18588506 | pubmed:issn | 1470-8728 | lld:pubmed |
| pubmed-article:18588506 | pubmed:author | pubmed-author:ReksSarah ESE | lld:pubmed |
| pubmed-article:18588506 | pubmed:author | pubmed-author:KelleyGrant... | lld:pubmed |
| pubmed-article:18588506 | pubmed:author | pubmed-author:LiXiangquanX | lld:pubmed |
| pubmed-article:18588506 | pubmed:author | pubmed-author:Kaproth-Josli... | lld:pubmed |
| pubmed-article:18588506 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18588506 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:18588506 | pubmed:volume | 415 | lld:pubmed |
| pubmed-article:18588506 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18588506 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18588506 | pubmed:pagination | 439-48 | lld:pubmed |
| pubmed-article:18588506 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:meshHeading | pubmed-meshheading:18588506... | lld:pubmed |
| pubmed-article:18588506 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18588506 | pubmed:articleTitle | Phospholipase C delta 1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity. | lld:pubmed |
| pubmed-article:18588506 | pubmed:affiliation | Department of Medicine, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. | lld:pubmed |
| pubmed-article:18588506 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18588506 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:18588506 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:18799 | entrezgene:pubmed | pubmed-article:18588506 | lld:entrezgene |
