TITLE

Regulation of the Insulin Gene by Glucose: Stimulation of Trans-Activation Potency of Human PDX-1 N-Terminal Domain

AUTHOR(S)
Shushan, Etti Ben; Cerasi, Erol; Melloul, Danielle
PUB. DATE
June 1999
SOURCE
DNA & Cell Biology;Jun99, Vol. 18 Issue 6, p471
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The beta cells in pancreatic islets of Langerhans increase insulin gene transcription in response to glucose. The pancreatic and duodenal homeobox-1 (PDX-1) plays a major role in glucose-induced insulin transcription. We studied the functional regions of the human PDX-1 protein fused to the DNA-binding domain of the transcription factor Gal4. The results indicate that the N-terminal domain of the hPDX-1, required for trans-activation (amino acids 1-120) in transfected betaTC6 and HeLa cells, is also regulated by extracellular glucose concentrations in transfected rat islets. Deletion analyses have led to the mapping of two regions within the N terminus that are essential for its trans-activation properties. One sequence spans amino acids 97-120 in transfected islet and HeLa cells or amino acids 77-120 in betaTC6 cells; the other includes the highly conserved B box (amino acids 31-41). We thus present evidence of a glucose effect on hPDX-1 trans-activation activity, in addition to the previously described regulatory effect on its DNA-binding activity.
ACCESSION #
6463029

 

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