Glucose stimulates the activation domain potential of the PDX‐1 homeodomain transcription factor

FEBS Letters - Tập 431 - Trang 362-366 - 1998
Helle V Petersen1, Mina Peshavaria2, Anette A Pedersen1, Jacques Philippe3, Roland Stein2, Ole D Madsen1, Palle Serup1
1Hagedorn Research Laboratory, Niels Steensens Vej 6, Gentofte 2820, Denmark
2Department of Molecular Physiology and Biopysics, Vanderbilt Medical Center, Nashville, TN 37232, USA
3Clinical Diabetology, Department of Medicine, CMU, 1, rue Michel Servet, CH-1211 Geneva 4, Switzerland

Tóm tắt

Glucose‐stimulated expression of the insulin gene in β cells is mediated by the PDX‐1 transcription factor. In this report, we show that stimulation results from effects on activation and DNA‐binding potential. Thus, glucose specifically stimulated expression in MIN6 β cells from chimeras of PDX‐1 and the GAL4 DNA‐binding domain which spanned the N‐terminal PDX‐1 activation domain located between amino acids 1 to 79. GAL4:PDX activity was induced over physiological glucose concentrations and was also regulated by effectors of this response. The level of endogenous PDX‐1 binding and phosphorylation were also induced under these conditions. We discuss how changes in PDX‐1 phosphorylation may influence activity in glucose‐treated β cells.


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