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Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2
Liora S Katz1, Yvan Gosmain, Eric Marthinet
1Division of Endocrinology, Diabetes and Nutrition, University Hospital, University of Geneva Medical School, 1211 Geneva, Switzerland. Liora.Katz@unige.ch
Molecular and Cellular Biology
|February 19, 2009
Summary
Pax6 is crucial for glucagon production in pancreatic alpha cells. It directly and indirectly regulates genes involved in glucagon synthesis and processing, including PC2 and 7B2.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Pax6 is essential for pancreatic development and regulates endocrine differentiation.
- Prohormone convertase 2 (PC2) and 7B2 are key for processing proglucagon into glucagon in alpha cells.
Purpose of the Study:
- To investigate the role of Pax6 in regulating glucagon biosynthesis and processing.
- To identify target genes controlled by Pax6 in pancreatic alpha cells.
Main Methods:
- Utilized small interfering RNA (siRNA) and dominant-negative Pax6 in InR1G9 alpha cells.
- Performed binding and transactivation studies to analyze gene regulation.
- Examined the expression of PC2 and 7B2 genes.
Main Results:
- Pax6 controls the expression of PC2 and 7B2 genes.
- Pax6 indirectly regulates PC2 transcription via cMaf and Beta2/NeuroD1.
- Pax6 directly and indirectly activates 7B2 gene expression through cMaf and Beta2/NeuroD1.
Conclusions:
- Pax6 is critical for glucagon biosynthesis and processing.
- Pax6 directly and indirectly activates glucagon, PC2, and 7B2 gene expression through cMaf and Beta2/NeuroD1.
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