Essential role of protein arginine methyltransferase 1 in pancreas development by regulating protein stability of neurogenin 3

Kanghoon Lee, Hyunki Kim, Joonyub Lee, Chang Myung Oh, Heein Song, Hyeongseok Kim, Seung Hoi Koo, Junguee Lee, Ajin Lim, Hail Kim

Research output: Contribution to journalArticle

Abstract

Background: Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated. Methods: Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells. Results: Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3. Conclusion: PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.

Original languageEnglish
Pages (from-to)649-658
Number of pages10
JournalDiabetes and Metabolism Journal
Volume43
Issue number5
DOIs
Publication statusPublished - 2019 Jan 1

Keywords

  • Diabetes mellitus; Islets of Langerhans; Neurog3 protein
  • Mouse
  • Mouse; Pancreas; Prmt1 protein

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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