دورية أكاديمية
Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.
| العنوان: | Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development. |
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| المؤلفون: | Padgett LR; Indiana Biosciences Research Institute, Indianapolis, IN, USA., Robertson MA; Department of Biology, Indiana University-Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA., Anderson-Baucum EK; Indiana Biosciences Research Institute, Indianapolis, IN, USA., Connors CT; Department of Biology, Indiana University-Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA., Wu W; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA., Mirmira RG; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.; Kovler Diabetes Center and the Department of Medicine, University of Chicago, Chicago, IL, USA., Mastracci TL; Indiana Biosciences Research Institute, Indianapolis, IN, USA.; Department of Biology, Indiana University-Purdue University-Indianapolis (IUPUI), Indianapolis, IN, USA.; Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 May; Vol. 35 (5), pp. e21473. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Organogenesis* , Protein Biosynthesis* , Protein Processing, Post-Translational*, Lysine/*analogs & derivatives , Oxidoreductases Acting on CH-NH Group Donors/*physiology , Pancreas, Exocrine/*cytology , Peptide Initiation Factors/*metabolism , RNA-Binding Proteins/*metabolism, Animals ; Cell Proliferation ; Female ; Lysine/biosynthesis ; Male ; Mice ; Mice, Knockout ; Pancreas, Exocrine/metabolism ; Peptide Initiation Factors/genetics ; RNA-Binding Proteins/genetics ; Eukaryotic Translation Initiation Factor 5A |
| مستخلص: | Pancreatic diseases including diabetes and exocrine insufficiency would benefit from therapies that reverse cellular loss and/or restore cellular mass. The identification of molecular pathways that influence cellular growth is therefore critical for future therapeutic generation. Deoxyhypusine synthase (DHPS) is an enzyme that post-translationally modifies and activates the mRNA translation factor eukaryotic initiation factor 5A (eIF5A). Previous work demonstrated that the inhibition of DHPS impairs zebrafish exocrine pancreas development; however, the link between DHPS, eIF5A, and regulation of pancreatic organogenesis remains unknown. Herein we identified that the conditional deletion of either Dhps or Eif5a in the murine pancreas results in the absence of acinar cells. Because DHPS catalyzes the activation of eIF5A, we evaluated and uncovered a defect in mRNA translation concomitant with defective production of proteins that influence cellular development. Our studies reveal a heretofore unappreciated role for DHPS and eIF5A in the synthesis of proteins required for cellular development and function. (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.) |
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| معلومات مُعتمدة: | P30 DK097512 United States DK NIDDK NIH HHS; R01 DK060581 United States DK NIDDK NIH HHS; R01 DK121987 United States DK NIDDK NIH HHS; R01 DK124906 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: DHPS; acinar cells; eIF5A; exocrine pancreas; hypusine biosynthesis; mRNA translation; translational regulation |
| المشرفين على المادة: | 0 (Peptide Initiation Factors) 0 (RNA-Binding Proteins) 3874VXF092 (hypusine) EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors) EC 1.5.1.- (deoxyhypusine synthase) K3Z4F929H6 (Lysine) |
| تواريخ الأحداث: | Date Created: 20210403 Date Completed: 20210720 Latest Revision: 20240327 |
| رمز التحديث: | 20240327 |
| مُعرف محوري في PubMed: | PMC8034418 |
| DOI: | 10.1096/fj.201903177R |
| PMID: | 33811703 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.201903177R |