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Titolo:
Insulin responsiveness of the glucagon gene conferred by interactions between proximal promoter and more distal enhancer-like elements involving the paired-domain transcription factor Pax6
Autore:
Grzeskowiak, R; Amin, J; Oetjen, E; Knepel, W;
Indirizzi:
Univ Gottingen, Dept Mol Pharmacol, D-37070 Gottingen, Germany Univ Gottingen Gottingen Germany D-37070 col, D-37070 Gottingen, Germany
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 39, volume: 275, anno: 2000,
pagine: 30037 - 30045
SICI:
0021-9258(20000929)275:39<30037:IROTGG>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CREB-BINDING-PROTEIN; CELL-SPECIFIC EXPRESSION; PANCREATIC-ISLET CELLS; RESPONSE ELEMENT; PHOSPHOENOLPYRUVATE CARBOXYKINASE; NUCLEAR-PROTEIN; MEMBRANE DEPOLARIZATION; PROGLUCAGON GENE; PATHO-PHYSIOLOGY; CYCLOSPORINE-A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
70
Recensione:
Indirizzi per estratti:
Indirizzo: Knepel, W Univ Gottingen, Dept Mol Pharmacol, Robert-Koch-Str 40,Postfach 3742, D-37070 Gottingen, Germany Univ Gottingen Robert-Koch-Str 40,Postfach3742 Gottingen Germany D-37070
Citazione:
R. Grzeskowiak et al., "Insulin responsiveness of the glucagon gene conferred by interactions between proximal promoter and more distal enhancer-like elements involving the paired-domain transcription factor Pax6", J BIOL CHEM, 275(39), 2000, pp. 30037-30045

Abstract

Regulation of gene transcription is an important aspect of insulin's action. However, the mechanisms involved are poorly understood. Insulin inhibitsglucagon gene transcription, and insulin deficiency is associated with hyperglucagonemia that contributes to hyperglycemia in diabetes mellitus. Transfecting glucagon-reporter fusion genes into a glucagon-producing pancreatic islet cell line, a 5'-, 3'-, and internal deletion analysis, and oligonucleotide cassette insertions failed in the present study to identify a single insulin-responsive element in the glucagon gene. They rather indicate that insulin responsiveness depends on the presence of both proximal promoter elements and more distal enhancer-like elements. When the paired domain transcription factor Pax6 binding sites within the proximal promoter element G1 and the enhancer-like element G3 were mutated into GAL4 binding sites, the expression of GAL4-Pax6 and GAL4-VP16 restored basal activity, whereas only GAL4-Pax6 restored also insulin responsiveness. Likewise, GAL4-CBP activity was inhibited by insulin within the glucagon promoter context. The results suggest that insulin responsiveness is conferred to the glucagon gene by the synergistic interaction of proximal promoter and more distal enhancer-like elements, with Pax6 and its potential coactivator the CREB-binding protein being critical components. These data thereby support concepts of insulin-responsive element-independent mechanisms of insulin action to inhibitgene transcription.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 01:49:25