Document Detail


A novel role for proline- and acid-rich basic region leucine zipper (PAR bZIP) proteins in the transcriptional regulation of a BH3-only proapoptotic gene.
MedLine Citation:
PMID:  17057225     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proline- and acid-rich (PAR) basic region leucine zipper (bZIP) proteins thyrotroph embryonic factor (TEF), D-site-binding protein (DBP), and hepatic leukemia factor have been involved in neurotransmitter homeostasis and amino acid metabolism. Here we demonstrate a novel role for these proteins in the transcriptional control of a BH3-only gene. PAR bZIP proteins are able to transactivate the promoter of bcl-gS. This promoter is particularly responsive to TEF activation and is silenced by NFIL3, a repressor that shares the consensus binding site with PAR bZIP proteins. Consistently, transfection of TEF induces the expression of endogenous bcl-gS in cancer cells, and this induction is independent of p53. A naturally occurring variant of DBP (tDBP), lacking the transactivation domain, has been identified and shown to impede the formation of active TEF dimers in a competitive manner and to reduce the TEF-dependent induction of bcl-gS. Of note, treatment of cancer cells with etoposide induces TEF activation and promotes the expression of bcl-gS. Furthermore, blockade of bcl-gS or TEF expression by a small interfering RNA strategy or transfection with tDBP significantly reduces the etoposide-mediated apoptotic cell death. These findings represent the first described role for PAR bZIP proteins in the regulation of a gene involved in the execution of apoptosis.
Authors:
Adalberto Benito; Olga Gutierrez; Carlos Pipaon; Pedro J Real; Frederic Gachon; Alistair E Ritchie; Jose L Fernandez-Luna
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-12     Completed Date:  2007-02-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38351-7     Citation Subset:  IM    
Affiliation:
Unidad de Genetica Molecular, Hospital Universitario Marques de Valdecilla, Servicio Cantabro de Salud, 39008 Santander, Spain.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / genetics*
Base Sequence
Cell Line
DNA Primers
Gene Expression Regulation*
Humans
Leucine Zippers / physiology*
Proline / physiology*
Promoter Regions, Genetic
Transcription, Genetic*
Chemical
Reg. No./Substance:
0/DNA Primers; 147-85-3/Proline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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