Pax6 Directly Down-Regulates Pcsk1n Expression Thereby Regulating PC1/3 Dependent Proinsulin Processing

PLoS ONE

Volumn 7, Issue 10, 2012, Pages

  Liu, Ting ^a   Zhao, Yanxia ^a   Tang, Na ^a   Feng, Ruopeng ^a   Yang, Xiaolong ^a   Lu, Nicole ^b   Wen, Jinhua ^a   Li, Lingsong ^a,b  

^a PEKING UNIVERSITY HEALTH SCIENCE CENTER   (China)

^b SHANGHAI ADVANCED RESEARCH INSTITUTE   (China)

Author keywords

[No Author keywords available]

Indexed keywords

LUCIFERASE; PROINSULIN; PROPROTEIN CONVERTASE 1; SMALL INTERFERING RNA; TRANSCRIPTION FACTOR PAX6;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DOWN REGULATION; EMBRYO; ENZYME ACTIVITY; ENZYME ASSAY; GEL MOBILITY SHIFT ASSAY; GENE; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE INTERACTION; GENE MUTATION; GENETIC TRANSFECTION; GLUCOSE METABOLISM; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PAX6 GENE; PCSK1 GENE; PROMOTER REGION; PROTEIN BINDING; PROTEIN CLEAVAGE; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REPORTER GENE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; WESTERN BLOTTING;

ANIMALS; DOWN-REGULATION; EYE PROTEINS; GENE KNOCKDOWN TECHNIQUES; HEK293 CELLS; HOMEODOMAIN PROTEINS; HUMANS; MICE; MUTATION; NERVE TISSUE PROTEINS; PAIRED BOX TRANSCRIPTION FACTORS; PROINSULIN; PROPROTEIN CONVERTASE 1; PROTEIN PROCESSING, POST-TRANSLATIONAL; REPRESSOR PROTEINS; RNA, SMALL INTERFERING;

EID: 84867287192     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0046934     Document Type: Article

References (36)

1. Mishra R, Gorlov IP, Chao LY, Singh S, Saunders GF, (2002) PAX6, paired domain influences sequence recognition by the homeodomain. J Biol Chem 277: 49488-49494.
2. Mansouri A, Hallonet M, Gruss P, (1996) Pax genes and their roles in cell differentiation and development. Curr Opin Cell Biol 8: 851-857.
3. Kozmik Z, Czerny T, Busslinger M, (1997) Alternatively spliced insertions in the paired domain restrict the DNA sequence specificity of Pax6 and Pax8. EMBO J 16: 6793-6803.
4. Sisodiya SM, Free SL, Williamson KA, Mitchell TN, Willis C, et al. (2001) PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. Nat Genet 28: 214-216.
5. Simpson TI, Price DJ, (2002) Pax6; a pleiotropic player in development. Bioessays 24: 1041-1051.
6. Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, et al. (2002) PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Diabetes 51: 224-230.
7. Sander M, Neubuser A, Kalamaras J, Ee HC, Martin GR, et al. (1997) Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev 11: 1662-1673.
8. Quiring R, Walldorf U, Kloter U, Gehring WJ, (1994) Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265: 785-789.
9. Ashery-Padan R, Zhou X, Marquardt T, Herrera P, Toube L, et al. (2004) Conditional inactivation of Pax6 in the pancreas causes early onset of diabetes. Dev Biol 269: 479-488.
10. Wen JH, Chen YY, Song SJ, Ding J, Gao Y, et al. (2009) Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3). Diabetologia 52: 504-513.
11. Zhu X, Zhou A, Dey A, Norrbom C, Carroll R, et al. (2002) Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proc Natl Acad Sci U S A 99: 10293-10298.
12. Zhu X, Orci L, Carroll R, Norrbom C, Ravazzola M, et al. (2002) Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3. Proc Natl Acad Sci U S A 99: 10299-10304.
13. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, et al. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16: 303-306.
14. Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, et al. (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112: 1550-1560.
15. Cameron A, Fortenberry Y, Lindberg I, (2000) The SAAS granin exhibits structural and functional homology to 7B2 and contains a highly potent hexapeptide inhibitor of PC1. FEBS Lett 473: 135-138.
16. Fricker LD, McKinzie AA, Sun J, Curran E, Qian Y, et al. (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J Neurosci 20: 639-648.
17. Qian Y, Devi LA, Mzhavia N, Munzer S, Seidah NG, et al. (2000) The C-terminal region of proSAAS is a potent inhibitor of prohormone convertase 1. J Biol Chem 275: 23596-23601.
18. Lanoue E, Day R, (2001) Coexpression of proprotein convertase SPC3 and the neuroendocrine precursor proSAAS. Endocrinology 142: 4141-4149.
19. Fortenberry Y, Hwang JR, Apletalina EV, Lindberg I, (2002) Functional characterization of ProSAAS: similarities and differences with 7B2. J Biol Chem 277: 5175-5186.
20. Boudreault A, Gauthier D, Rondeau N, Savaria D, Seidah NG, et al. (1998) Molecular characterization, enzymatic analysis, and purification of murine proprotein convertase-1/3 (PC1/PC3) secreted from recombinant baculovirus-infected insect cells. Protein Expr Purif 14: 353-366.
21. Wei S, Feng Y, Che FY, Pan H, Mzhavia N, et al. (2004) Obesity and diabetes in transgenic mice expressing proSAAS. J Endocrinol 180: 357-368.
22. Mayes DA, Hu Y, Teng Y, Siegel E, Wu X, et al. (2006) PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene. Cancer Res 66: 9809-9817.
23. Zhou YH, Hu Y, Mayes D, Siegel E, Kim JG, et al. (2010) PAX6 suppression of glioma angiogenesis and the expression of vascular endothelial growth factor A. J Neurooncol. 96: 191-200.
24. Jang ES, Goldman JE, (2011) Pax6 expression is sufficient to induce a neurogenic fate in glial progenitors of the neonatal subventricular zone. PLoS One 6: e20894.
25. Apletalina E, Appel J, Lamango NS, Houghten RA, Lindberg I, (1998) Identification of inhibitors of prohormone convertases 1 and 2 using a peptide combinatorial library. J Biol Chem 273: 26589-26595.
26. Cameron A, Appel J, Houghten RA, Lindberg I, (2000) Polyarginines are potent furin inhibitors. J Biol Chem 275: 36741-36749.
27. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, et al. (2005) MatInspector and beyond: promoter analysis based on transcription factor binding sites. Bioinformatics 21: 2933-2942.
28. Epstein J, Cai J, Glaser T, Jepeal L, Maas R, (1994) Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes. J Biol Chem 269: 8355-8361.
29. Morgan DJ, Wei S, Gomes I, Czyzyk T, Mzhavia N, et al. (2010) The propeptide precursor proSAAS is involved in fetal neuropeptide processing and body weight regulation. J Neurochem 113: 1275-1284.
30. Katz LS, Gosmain Y, Marthinet E, Philippe J, (2009) Pax6 regulates the proglucagon processing enzyme PC2 and its chaperone 7B2. Mol Cell Biol 29: 2322-2334.
31. Gosmain Y, Marthinet E, Cheyssac C, Guerardel A, Mamin A, et al. (2010) Pax6 controls the expression of critical genes involved in pancreatic {alpha} cell differentiation and function. J Biol Chem 285: 33381-33393.
32. Gosmain Y, Katz LS, Masson MH, Cheyssac C, Poisson C, et al. (2012) Pax6 is crucial for beta-cell function, insulin biosynthesis, and glucose-induced insulin secretion. Mol Endocrinol 26: 696-709.
33. Hohmeier HE, Newgard CB, (2004) Cell lines derived from pancreatic islets. Mol Cell Endocrinol 228: 121-128.
34. Clark JD, Gebhart GF, Gonder JC, Keeling ME, Kohn DF, (1997) Special Report: The 1996 Guide for the Care and Use of Laboratory Animals. ILAR J 38: 41-48.
35. Hori H, Gu YJ, Nagata N, Balamurugan AN, Satake A, et al. (2001) Isolation, culture, and characterization of endocrine cells from 6-month-old porcine pancreas. Cell Transplant 10: 459-464.
36. Lamango NS, Zhu X, Lindberg I, (1996) Purification and enzymatic characterization of recombinant prohormone convertase 2: stabilization of activity by 21 kDa 7B2. Arch Biochem Biophys 330: 238-250.