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.

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.
Authors	Adalberto Benito, Olga Gutierrez, Carlos Pipaon, Pedro J Real, Frederic Gachon, Alistair E Ritchie, Jose L Fernandez-Luna
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 50 Pg. 38351-7 (Dec 15 2006) ISSN: 0021-9258 [Print] United States
PMID	17057225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA Primers Proline
Topics	Apoptosis (genetics) Base Sequence Cell Line DNA Primers Gene Expression Regulation Humans Leucine Zippers (physiology) Proline (physiology) Promoter Regions, Genetic Transcription, Genetic

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