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.

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Version: Final published version
Serval ID
serval:BIB_2537B241A10D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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.
Journal
Journal of Biological Chemistry
Author(s)
Benito A., Gutierrez O., Pipaon C., Real P.J., Gachon F., Ritchie A.E., Fernandez-Luna J.L.
ISSN
0021-9258
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
281
Number
50
Pages
38351-38357
Language
english
Abstract
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.
Keywords
Apoptosis/genetics, Base Sequence, Cell Line, DNA Primers, Gene Expression Regulation, Humans, Leucine Zippers/physiology, Proline/physiology, Promoter Regions, Genetic, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
01/10/2009 14:10
Last modification date
20/08/2019 13:03
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