PDX1
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RefSeq (protein) | |||||||||
Location (UCSC) | Chr 13: 27.92 – 27.93 Mb | Chr 5: 147.21 – 147.21 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
PDX1 (pancreatic and duodenal homeobox 1), also known as insulin promoter factor 1, is a
Function
Pancreatic development
In
Pdx1 is accepted as the earliest marker for pancreatic differentiation, with the fates of pancreatic cells controlled by downstream transcription factors.
β-cell maturation and survival
The final stages of pancreas development involves the production of different
In the mature pancreas, Pdx1 expression seems to be required for the maintenance and survival of β-cells. For instance, experimentally reducing the level of Pdx1 expression at this stage makes β-cells produce higher amounts of glucagon,[15] suggesting that Pdx1 inhibits the conversion of β-cells into α-cells. Furthermore, Pdx1 appears to be important in mediating the effect of insulin on the apoptotic programmed cell death of β-cells: a small concentration of insulin protects β-cells from apoptosis, but not in cells where Pdx1 expression has been inhibited.[16][17]
Duodenum
Pdx1 is necessary for the development of the proximal duodenum and maintenance of the gastro-duodenal junction.
Pathology
Experiments in animal models have shown that a reduction in Pdx1 expression can cause symptoms that are characteristic of
Interactions
Pdx1 has been shown to
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000139515 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029644 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Brooke, N. M., Garcia-Fernàndez, J., & Holland, P. W. (1998). The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster. Nature, 392(6679), 920.
- ^ "PDX1". HGNC. Retrieved 22 April 2016.
- PMID 7590740.
- ^ Wright, C. V., Schnegelsberg, P., & De Robertis, E. M. (1989). XlHbox 8: a novel Xenopus homeo protein restricted to a narrow band of endoderm. Development, 105(4), 787-794.
- ^ "OrthoMaM phylogenetic marker: PDX1 coding sequence". OrthoMam v10. 2019. Retrieved 24 February 2019.
- PMID 20463047.
- ^ S2CID 11040949.
- ^ S2CID 4379651.
- ^ PMID 18335054.
- ^ Gannon M, Ables ET, Crawford L, et al. pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol. 2007;314(2):406-17. doi:10.1016/j.ydbio.2007.10.038
- ^ Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes. Genes Dev. 1998;12(12):1763-8.
- PMID 12697734.
- PMID 17158802.
- ^ PMID 23873371.
- PMID 22135308.
- ^ Fujimoto, Kei, and Kenneth S. Polonsky. "Pdx1 and other factors that regulate pancreatic β‐cell survival." Diabetes, Obesity and Metabolism 11 (2009): 30-37.
- PMID 18477649.
- ^ "Entrez Gene: PDX1 pancreatic and duodenal homeobox 1".
- PMID 11575290.
- PMID 28674003.
- PMID 15665000.
Further reading
- Zhou Q, Brown J, Kanarek A, Rajagopal J, Douglas A, Melton DA (2008). "In vivo reprogramming of adult pancreatic exocrine cells to β-cells". Nature. 455 (7213): 627–32. S2CID 205214877.
- Hui H, Perfetti R (2002). "Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood". Eur. J. Endocrinol. 146 (2): 129–41. PMID 11834421.
- Leonard J, Peers B, Johnson T, et al. (1994). "Characterization of somatostatin transactivating factor-1, a novel homeobox factor that stimulates somatostatin expression in pancreatic islet cells". Mol. Endocrinol. 7 (10): 1275–83. PMID 7505393.
- Stoffel M, Stein R, Wright CV, et al. (1995). "Localization of human homeodomain transcription factor insulin promoter factor 1 (IPF1) to chromosome band 13q12.1". Genomics. 28 (1): 125–6. PMID 7590740.
- Inoue H, Riggs AC, Tanizawa Y, et al. (1996). "Isolation, characterization, and chromosomal mapping of the human insulin promoter factor 1 (IPF-1) gene". Diabetes. 45 (6): 789–94. PMID 8635654.
- Waeber G, Thompson N, Nicod P, Bonny C (1997). "Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor". Mol. Endocrinol. 10 (11): 1327–34. PMID 8923459.
- Watada H, Kajimoto Y, Kaneto H, et al. (1997). "Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription". Biochem. Biophys. Res. Commun. 229 (3): 746–51. PMID 8954967.
- Marshak S, Totary H, Cerasi E, Melloul D (1997). "Purification of the beta-cell glucose-sensitive factor that transactivates the insulin gene differentially in normal and transformed islet cells". Proc. Natl. Acad. Sci. U.S.A. 93 (26): 15057–62. PMID 8986763.
- Stoffers DA, Zinkin NT, Stanojevic V, et al. (1997). "Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence". Nat. Genet. 15 (1): 106–10. S2CID 25406130.
- Sharma S, Jhala US, Johnson T, et al. (1997). "Hormonal regulation of an islet-specific enhancer in the pancreatic homeobox gene STF-1". Mol. Cell. Biol. 17 (5): 2598–604. PMID 9111329.
- Carty MD, Lillquist JS, Peshavaria M, et al. (1997). "Identification of cis- and trans-active factors regulating human islet amyloid polypeptide gene expression in pancreatic beta-cells". J. Biol. Chem. 272 (18): 11986–93. PMID 9115263.
- Macfarlane WM, Smith SB, James RF, et al. (1997). "The p38/reactivating kinase mitogen-activated protein kinase cascade mediates the activation of the transcription factor insulin upstream factor 1 and insulin gene transcription by high glucose in pancreatic beta-cells". J. Biol. Chem. 272 (33): 20936–44. PMID 9252422.
- Macfarlane WM, Frayling TM, Ellard S, et al. (1999). "Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes". J. Clin. Invest. 104 (9): R33–9. PMID 10545530.
- Hani EH, Stoffers DA, Chèvre JC, et al. (1999). "Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus". J. Clin. Invest. 104 (9): R41–8. PMID 10545531.
- Glick E, Leshkowitz D, Walker MD (2000). "Transcription factor BETA2 acts cooperatively with E2A and PDX1 to activate the insulin gene promoter". J. Biol. Chem. 275 (3): 2199–204. PMID 10636926.
- Schwartz PT, Perez-Villamil B, Rivera A, et al. (2000). "Pancreatic homeodomain transcription factor IDX1/IPF1 expressed in developing brain regulates somatostatin gene transcription in embryonic neural cells". J. Biol. Chem. 275 (25): 19106–14. PMID 10751390.
- Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. PMID 11076863.
- Liu Y, MacDonald RJ, Swift GH (2001). "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer and cooperation with a pancreas-specific basic helix-loop-helix complex". J. Biol. Chem. 276 (21): 17985–93. PMID 11279116.
- Samaras SE, Cissell MA, Gerrish K, et al. (2002). "Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6". Mol. Cell. Biol. 22 (13): 4702–13. PMID 12052878.
- Zhou J, Pineyro MA, Wang X, et al. (2002). "Exendin-4 differentiation of a human pancreatic duct cell line into endocrine cells: involvement of PDX-1 and HNF3beta transcription factors". J. Cell. Physiol. 192 (3): 304–14. S2CID 11530928.
External links
- GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus
- PDX1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.