Pax6 Regulates the Proglucagon Processing Enzyme PC2 and Its Chaperone 7B2▿ †

Autor: Jacques Philippe, Liora S. Katz, Yvan Gosmain, Eric Marthinet
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Transcriptional Activation
endocrine system
PAX6 Transcription Factor
Prohormone convertase
Proprotein convertase 2
Gene Expression Regulation/*physiology
Nerve Tissue Proteins
Biology
Proglucagon
Glucagon
Paired Box Transcription Factors/*physiology
Alpha cell
Cell Line
Transactivation
Neuroendocrine Secretory Protein 7B2
Molecular Chaperones/genetics/metabolism
Proto-Oncogene Proteins c-maf/genetics
Repressor Proteins/*physiology
Cricetinae
Basic Helix-Loop-Helix Transcription Factors
Nerve Tissue Proteins/genetics
Proprotein Convertase 2/*genetics
Animals
Paired Box Transcription Factors
Eye Proteins
Molecular Biology
Transcription factor
Proglucagon/metabolism
Regulation of gene expression
ddc:616
Homeodomain Proteins
Basic Helix-Loop-Helix Transcription Factors/genetics
Homeodomain Proteins/*physiology
Cell Biology
Articles
Molecular biology
eye diseases
Cell biology
Repressor Proteins
Glucagon/biosynthesis
Proprotein Convertase 2
Gene Expression Regulation
Proto-Oncogene Proteins c-maf
Neuroendocrine Secretory Protein 7B2/*genetics
Eye Proteins/*physiology
sense organs
Molecular Chaperones
Zdroj: Molecular and Cellular Biology, Vol. 29, No 8 (2009) pp. 2322-2334
ISSN: 0270-7306
Popis: Pax6 is important in the development of the pancreas and was previously shown to regulate pancreatic endocrine differentiation, as well as the insulin, glucagon, and somatostatin genes. Prohormone convertase 2 (PC2) is the main processing enzyme in pancreatic alpha cells, where it processes proglucagon to produce glucagon under the spatial and temporal control of 7B2, which functions as a molecular chaperone. To investigate the role of Pax6 in glucagon biosynthesis, we studied potential target genes in InR1G9 alpha cells transfected with Pax6 small interfering RNA and in InR1G9 clones expressing a dominant-negative form of Pax6. We now report that Pax6 controls the expression of the PC2 and 7B2 genes. By binding and transactivation studies, we found that Pax6 indirectly regulates PC2 gene transcription through cMaf and Beta2/NeuroD1 while it activates the 7B2 gene both directly and indirectly through the same transcription factors, cMaf and Beta2/NeuroD1. We conclude that Pax6 is critical for glucagon biosynthesis and processing by directly and indirectly activating the glucagon gene through cMaf and Beta2/NeuroD1, as well as the PC2 and 7B2 genes.
Databáze: OpenAIRE