Linked Life Data

16288006

Source:http://linkedlifedata.com/resource/pubmed/id/16288006

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2005-11-18
pubmed:abstractText
hSNF5, the smallest member of the SWI/SNF chromatin remodeling complex, is lost in most malignant rhabdoid tumors (MRT). In MRT cell lines, reexpression of hSNF5 induces G1 cell cycle arrest, elevated p16INK4a, and activated replicative senescence markers, such as beta-galactosidase (beta-Gal) and plasminogen activator inhibitor-1. To compare the replicative senescence caused by hSNF5 in A204 cells to normal cellular senescence, we examined the activation of both p16INK4a and p21CIP/WAF1. Analogous to normal cellular senescence, both p16INK4a and p21CIP/WAF1 were up-regulated following hSNF5 restoration. Furthermore, we found that hSNF5 bound the p16INK4a and p21CIP/WAF1 promoters, suggesting that it directly regulates transcription of these genes. Using p16INK4a RNA interference, we showed its requirement for the replicative senescence caused by hSNF5 but not the growth arrest. Instead, p21CIP/WAF1 remained activated by hSNF5 in the absence of high p16INK4a expression, apparently causing the growth arrest in A204. Interestingly, we also found that, in the absence of p16INK4a, reexpression of hSNF5 also increased protein levels of a second cyclin-dependent kinase (CDK) inhibitor, p18INK4c. However, our data show that lack of hSNF5 does not abrogate cellular responsiveness to DNA damage or growth-inhibitory factors. In summary, our studies suggest that hSNF5 loss may influence the regulation of multiple CDK inhibitors involved in replicative senescence.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10192-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16288006-Cell Aging, pubmed-meshheading:16288006-Cell Growth Processes, pubmed-meshheading:16288006-Cell Line, Tumor, pubmed-meshheading:16288006-Chromosomal Proteins, Non-Histone, pubmed-meshheading:16288006-Cyclin-Dependent Kinase Inhibitor p16, pubmed-meshheading:16288006-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:16288006-DNA-Binding Proteins, pubmed-meshheading:16288006-Fibroblasts, pubmed-meshheading:16288006-Gene Deletion, pubmed-meshheading:16288006-Gene Expression Regulation, pubmed-meshheading:16288006-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16288006-Genes, p16, pubmed-meshheading:16288006-Humans, pubmed-meshheading:16288006-Rhabdoid Tumor, pubmed-meshheading:16288006-Transcription Factors, pubmed-meshheading:16288006-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Loss of the hSNF5 gene concomitantly inactivates p21CIP/WAF1 and p16INK4a activity associated with replicative senescence in A204 rhabdoid tumor cells.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7295, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural