Linked Life Data

12020819

Source:http://linkedlifedata.com/resource/pubmed/id/12020819

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2002-5-21
pubmed:abstractText
Apobec-1 catalyzes C to U editing of apolipoprotein B (apoB) mRNA in the mammalian intestine. Rat apobec-1 is transcribed from three distinct promoters, which contain distinct 5' untranslated regions (5'UTRs) accompanied by variable numbers of in-frame upstream AUGs (uAUGs). We have observed a shift in apobec-1 promoter usage in an experimental model of colon carcinogenesis, resulting in transcripts loaded with 5'AUGs. In colon cancer, apobec-1 protein levels decreased by 90% in the cancer tissue as compared to normal tissue, suggesting an inhibitory effect of the 5'UTR on apobec-1 translation. We investigated the effects of these different 5'UTRs by site-directed mutagenesis coupled with in vitro translation studies. These studies established that the uAUGs within the 5'UTR of the alternative transcripts inhibit apobec-1 translation. This effect was independent of the length of the 5'UTR. Further analysis demonstrated that these uAUGs altered the polysome distribution, shifting the mRNA towards a denser, post-polyribosomal fraction. These findings were confirmed in transient transfection studies in vivo using HepG2 cells, where functional expression of apobec-1 was restored by mutagenesis of the uAUGs. Taken together, these data imply that rat apobec-1 gene expression is downregulated through alternative promoter usage. This dominant translational control of apobec-1 gene expression is most plausibly exerted through uAUGs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
1575
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-62
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Apobec-1 transcription in rat colon cancer: decreased apobec-1 protein production through alterations in polysome distribution and mRNA translation associated with upstream AUGs.
pubmed:affiliation
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, Campus Box 8124, 660 South Euclid Avenue, St. Louis, MO 63110, USA. sanant@im.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't