Linked Life Data

17804813

Source:http://linkedlifedata.com/resource/pubmed/id/17804813

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2007-10-26
pubmed:abstractText
Maintenance of intestinal mucosal epithelial integrity requires polyamines that modulate the expression of various genes involved in cell proliferation and apoptosis. Recently, polyamines were shown to regulate the subcellular localization of the RNA-binding protein HuR, which stabilizes its target transcripts such as nucleophosmin and p53 mRNAs. The activating transcription factor-2 (ATF-2) mRNA encodes a member of the ATF/CRE-binding protein family of transcription factors and was computationally predicted to be a target of HuR. Here, we show that polyamines negatively regulate ATF-2 expression posttranscriptionally and that polyamine depletion stabilizes ATF-2 mRNA by enhancing the interaction of the 3'-untranslated region (UTR) of ATF-2 with cytoplasmic HuR. Decreasing cellular polyamines by inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine increased the levels of ATF-2 mRNA and protein, whereas increasing polyamines by ectopic ODC overexpression repressed ATF-2 expression. Polyamine depletion did not alter transcription via the ATF-2 gene promoter but increased the stability of ATF-2 mRNA. Increased cytoplasmic HuR in polyamine-deficient cells formed ribonucleoprotein complexes with the endogenous ATF-2 mRNA and specifically bound to 3'-UTR of ATF-2 mRNA on multiple nonoverlapping 3'-UTR segments. Adenovirus-mediated HuR overexpression elevated ATF-2 mRNA and protein levels, whereas HuR silencing rendered the ATF-2 mRNA unstable and prevented increases in ATF-2 mRNA and protein. Furthermore, inhibition of ATF-2 expression prevented the increased resistance of polyamine-deficient cells to apoptosis induced by treatment with tumor necrosis factor-alpha and cycloheximide. These results indicate that polyamines modulate the stability of ATF-2 mRNA by altering cytoplasmic HuR levels and that polyamine-modulated ATF-2 expression plays a critical role in regulating epithelial apoptosis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-11289308, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-11292836, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-11402335, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-11533243, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-11856372, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-12198703, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-12663670, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-12821781, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-12963828, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-13678416, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-14981256, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15010535, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15024023, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15257295, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15510159, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15574764, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15781626, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15861128, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-15916964, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-16202210, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-16354757, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-16690610, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-16706751, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-16996249, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-1702074, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17079470, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17253961, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17404803, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17442733, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17464296, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17534146, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-17558654, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-1827203, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-2138707, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-2928784, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-3282244, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-5432063, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-7737129, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-8382609, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-88453, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-9628881, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-9779995, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-9812896, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-9819389, http://linkedlifedata.com/resource/pubmed/commentcorrection/17804813-9858769
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1059-1524
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4579-90
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
More...