Identification of β-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA

• Martin Olbrot

  Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215; Department of Physiology, Tufts University, Boston, MA 02111; and Department of Medicine, Harvard Medical School, Boston, MA 02215

• Jonathan Rud

  Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215; Department of Physiology, Tufts University, Boston, MA 02111; and Department of Medicine, Harvard Medical School, Boston, MA 02215

• Larry G. Moss

  Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215; Department of Physiology, Tufts University, Boston, MA 02111; and Department of Medicine, Harvard Medical School, Boston, MA 02215

• Arun Sharma

  Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215; Department of Physiology, Tufts University, Boston, MA 02111; and Department of Medicine, Harvard Medical School, Boston, MA 02215

抄録

Of the three critical enhancer elements that mediate β-cell-specific and glucose-responsive expression of the insulin gene, only the identity of the transcription factor binding to the RIPE3b element (RIPE3b1) has remained elusive. Using a biochemical purification approach, we have identified the RIPE3b1 factor as a m ammalian homologue of avian MafA /L-Maf (mMafA). The avian MafA is a cell-type determination factor that expressed ectopically can trigger lens differentiation program, but no mammalian homologue of avian MafA has previously been identified. Here, we report cloning of the human mafA (hMafA) and demonstrate that it can specifically bind the insulin enhancer element RIPE3b and activate insulin-gene expression. In addition, mMafA has a very restrictive cellular distribution and is selectively expressed in pancreatic β but not in α cells. We suggest that mMafA has an essential role in the function and differentiation of β-cells and thus may be associated with the pathophysiological origins of diabetes.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 99 (10), 6737-6742, 2002-05-14

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363388844568174336
• NII論文ID: 80015436371
• DOI: 10.1073/pnas.102168499
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.102168499
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