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

B. Yan, Nina Raben, Paul Plotz

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)29760-29764
Number of pages5
JournalJournal of Biological Chemistry
Issue number33
StatePublished - Aug 16 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1 signaling pathway.'. Together they form a unique fingerprint.

Cite this