Tissue-specific and glucose-responsive expression of the pancreatic derived factor (PANDER) promoter.
Biochim Biophys Acta
; 1730(3): 215-25, 2005 Sep 25.
Article
de En
| MEDLINE
| ID: mdl-16102856
ABSTRACT
Pancreatic derived factor (PANDER) is a recently identified cytokine-like protein that is dominantly expressed in the islets of Langerhans of the pancreas. To investigate the mechanism of tissue-specific regulation of PANDER, we identified and characterized the promoter region. The transcriptional start site was identified 520 bp upstream of the translational start codon by 5'-RLM-RACE. Computer algorithms identified several islet-associated and glucose-responsive binding motifs that included A and E boxes, hepatocyte nuclear factors 1 and 4, Oct-1, and signal transducer and activator of transcription 3, and 5. Reporter gene analysis revealed cell type-specific PANDER promoter expression in islet and liver-derived cell lines. Levels of PANDER mRNA were directly concordant to the observed cell type-specific PANDER promoter gene expression. The minimal element was mapped to the 5'-UTR and located between +200 and +491 relative to the transcriptional start site and imparted maximal gene expression. In addition, several putative glucose-responsive binding sites were further functionally characterized to reveal critical regulatory elements of PANDER. The PANDER promoter was demonstrated to be glucose-responsive in a dose-dependent manner in murine insulinoma beta-TC3 cells and primary murine islets, but unresponsive in glucagon-secreting alpha-TC3 cells. Our findings revealed that the 5'-UTR of PANDER contains the minimal element for gene expression and imparts both tissue-specificity and glucose-responsiveness. The regulation of PANDER gene expression mimics that of insulin and suggests a potential biological function of PANDER involved in metabolic homeostasis.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pancréas
/
Cytokines
/
Ilots pancréatiques
/
Régions promotrices (génétique)
/
Glucose
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Biochim Biophys Acta
Année:
2005
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique