RGD Reference Report - The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1 signaling pathway. - Rat Genome Database

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The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1 signaling pathway.

Authors: Yan, B  Raben, N  Plotz, P 
Citation: Yan B, etal., J Biol Chem 2002 Aug 16;277(33):29760-4. Epub 2002 Jun 13.
RGD ID: 1302856
Pubmed: PMID:12065598   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M204721200   (Journal Full-text)

Acid alpha-glucosidase (GAA) is a lysosomal enzyme that degrades glycogen. A deficiency of GAA is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenosis type II. Previously, we identified an intronic repressor element in the GAA gene and demonstrated that Hes-1, a basic helix-loop-helix factor, binds to a C class E box within the element and functions as a transcriptional repressor in HepG2 cells. Hes-1 is a well studied downstream target gene in the Notch signaling pathway. In this study, over-expression and depletion of Notch-1 intracellular domain (NICD) strategies were used to investigate whether expression of the GAA gene is under the control of Notch-1/Hes-1 signaling. In co-transfection experiments, Hes-1, up-regulated by over-expressed NICD, enhanced the repressive effect of the DNA element with wild type Hes-1 binding sites but not with mutant Hes-1 binding sites. Conversely, depletion of Notch-1 with phosphorothioated antisense oligonucleotides, corresponding to the fourth ankyrin repeat within NICD, led to reduced Hes-1. Constitutively over-expressed Hes-1 and Notch-1 repressed GAA gene expression. Therefore, our data establish that the human GAA gene, encoding a lysosomal enzyme, is a downstream target of the Notch-1/Hes-1 signaling pathway.

Objects referenced in this article
Gene Gaa alpha glucosidase Rattus norvegicus

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