IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
INSULIN DEGRADING ENZYME CORE PROMOTER IS REGULATED BY NRF-1 AND RELATED-ETS TRANSCRIPTION FACTORS
Autor/es:
LEAL MC; CASTAÑO EM; MORELLI L
Lugar:
Puerto Madryn
Reunión:
Congreso; Insulin-degrading enzyme core promoter is regulated by NRF1 and related ETS transcription factors; 2010
Institución organizadora:
Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular
Resumen:
Insulin Degrading Enzyme (IDE) is a conserved metallopeptidase that contributes in the in vivo metabolism of cerebral insulin and amyloid â peptide (Aâ) of Alzheimer’s disease (AD). IDE mRNA and activity levels are decreased in AD brain, but its transcripts levels increased in cultures of primary rat astrocytes exposed to fibrillar Aâ. Despite its involvement in insulin and Aâ peptide clearance, little is known about the regulation of IDE expression. Aims: To characterize the core promoter of human IDE gene. Methods: in silico analysis; 5’RACE; U87MG and HeLa cell lines transfections; promoter deletions in pGL3-luciferase; site-directed mutagenesis; EMSA. Results: 1-IDE 5’ sequence lacks a canonical sequence with promoter function. 2-IDE shows several transcription start sites from -39 to 28 that may lead to the generation of different protein isoforms. 3-The promoter construct -120/59-luc, containing canonical sequences for NRF-1 and ETS family, showed the highest transcriptional activity. 4-Mutation of the putative NRF1-binding site abolished transcription of the reporter gene and mutation of ETS site resulted in a 75% decrease compared to control; 5-NRF1 and Ets1, a member of ETS family, bind to the predicted sequence in vitro. Conclusions: the mitochondrial biogenesis regulator-NRF1 and ETS likely drive IDE transcriptionmodulating IDE expression and subcellular localization