Linked Life Data

8649841

Source:http://linkedlifedata.com/resource/pubmed/id/8649841

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1996-7-25
pubmed:abstractText
The bcl-2 gene becomes activated in many types of human cancers and contributes to neoplastic cell expansion, as well as to resistance to radiation and chemotherapy, by blocking programmed cell death or apoptosis. The expression of this proto-oncogene is regulated at both the transcriptional and post-transcriptional levels. DNA sequence comparisons of human, mouse, rat and chicken bcl-2 cDNAs revealed the presence of an open reading frame (ORF) [correction of (OFR)] located upstream of the normal coding region. Because upstream ORFs (uORFs) have been associated with translational repression, we analysed the functional significance of the 11 amino-acid uORF in the human BCL-2 gene (-119 to -84 bp). Deletion of this uORF from chloramphenicol acetyltransferase (CAT) reporter gene constructs that contained the bcl-2 promoter and entire 5'-untranslated region (5'-UTR), as well as introduction of an A-->T mutation at position -119 bp that destroyed the AUG-initiation codon, significantly increased CAT activity in HeLa, CEM, and other cell lines, without producing a corresponding elevation in CAT mRNA levels. Positioning this uORF, together with its accompanying Kozak sequences, between a heterologous promoter from SV40 and a CAT reporter gene resulted in marked inhibition of CAT protein production without a decrease in CAT mRNA. Mutation of the start codon (ATG-->TTG) of this uORF completely abolished its inhibitory activity, consistent with a translational mechanism. Taken together, these findings suggest that the uORF located within the 5'UTR of the bcl-2 gene is necessary and sufficient for translational regulation of bcl-2 gene expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1369-74
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
A cis-acting element in the BCL-2 gene controls expression through translational mechanisms.
pubmed:affiliation
La Jolla Cancer Research Foundation, Oncogene & Tumor Suppressor Gene Program, California 92037, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't