title: Mutant PAX6 downregulates prohormone convertase 2 expression in mouse islets.
abstract: Transcriptional factor paired box 6 (PAX6) is very important for the development of the eyes, central nervous system, and pancreas. PAX6 mutations are associated with a diabetic phenotype and abnormal glucose metabolism. Our previous study showed that PAX6 directly bound to and activated the prohormone convertase 1/3 (Pc1/3) gene promoter and subsequently regulated proinsulin processing. Prohormone convertase 2 (PC2) is the essential enzyme for pancreatic proinsulin processing. To study the regulation of PAX6 in Pc2 expression, we did research on the pancreas of Pax6 R266Stop mutant mice, where truncated mutations happened in the C-terminal of the PAX6 protein. Our studies showed that the mutant PAX6 protein was stable and regulated the activity of Pc2 promoter as shown by luciferase activity assays. We found that the wild-type PAX6 protein imparts a transcriptional effect, and the mutant PAX6 can also regulate the downstream molecules. The results provide new insights into the mechanism of truncated PAX6 in regulating the functions of the pancreas and endocrine system.
authors.affiliation: Peking University Stem Cell Research Center, and Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Wenwan
authors.initials: W
authors.lastname: Cao
authors.forename: Shixin
authors.initials: S
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wen
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D005136:Eye Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D045706:Proprotein Convertase 2 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C473668:Pcsk2 protein, mouse; D045706:Proprotein Convertase 2
keywords: PAX6; Pc2 gene; islets