Toward understanding the glucose- -cells from analysis of glucose-responsive MafA kinase

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: KATAOKA Kohsuke 奈良先端科学技術大学院大学, バイオサイエンス研究科, 准教授 (20262074)
• Project Period (FY): 2010 – 2012
• Keywords: エネルギー・糖質代謝異常・細胞内シグナル伝達・遺伝子発現制御

Research Abstract

We have found that multiple phosphorylation events on MafA transcription factor by GSK3 and MaCK are required for its function in β-cells through enhancing DNA-binding and Beta2 association. Furthermore, We demonstrated that decreased MafA phosphorylation is one of the main causes of β-cell dysfunction in type II diabetes. We also identified a small molecule inhibitor that mimics endogenous MafA de-phosphorylation in β-cells. These findings led to understanding of molecular mechanisms of β-cell function and dysfunction.

Research Products

• [Journal Article] ATF2 interacts with β-cell enriched transcription factors, MafA, Pdx1, and Beta2, and activates insulin gene transcription. (2011)
  • Author(s): Han, S.-i., K. Yasuda, and K. Kataoka
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 10449-10456
  • DOI: DOI:10.1074/jbc.M110.209510
• [Journal Article] Proteasome activator PA28γ stimulates degradation of GSK3-phosphorylated insulin transcription activator MAFA (2011)
  • Author(s): Kanai, K., S. Aramata, S. Katakami, K. Yasuda, and K. Kataoka
  • Journal Title: J. Mol. Endocrinol Volume: 47 Pages: 119-127
  • DOI: DOI:10.1530/JME-11-0044
• [Journal Article] MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development (2011)
  • Author(s): Kamitani-Kawamoto, A., M. Hamada, T. Moriguchi, M. Miyai, F. Saji, I. Hatamura, K. Nishikawa, H. Takayanagi, S. Hitoshi, K. Ikenaka, T. Hosoya, Y. Hotta, S. Takahashi, and K. Kataoka
  • Journal Title: J. Bone Miner. Res Volume: 26 Pages: 2463-2472
  • DOI: DOI:10.1002/jbmr.458
• [Journal Article] Insulin transactivator MafA regulates intra-thymic expression of insulin and affects susceptibility to type I diabetes (2010)
  • Author(s): Noso, S., K. Kataoka, Y. Kawabata, N. Babaya, Y. Hiromine, K. Yamaji, Y. Fujisawa, S. Aramata, T. Kudo, S. Takahashi, and H. Ikegami
  • Journal Title: Diabetes Volume: 59 Pages: 2579-2587
  • DOI: DOI:10.2337/db.10-0476
• [Journal Article] SUMOylation negatively regulates transcriptional and oncogenic activities of MafA (2010)
  • Author(s): Kanai K., H.M. Reza, A. Kamitani, Y. Hamazaki, S.-i. Han, K. Yasuda, and K. Kataoka
  • Journal Title: Genes Cells Volume: 15 Pages: 971-982
  • DOI: DOI:10.1111/j.1365-2443
• [Presentation] Phosphorylations regulate transcriptional and non-transcriptional activity of MafA in oncogenic transformation (2010)
  • Author(s): K. Kanai
  • Organizer: 9thEMBL Conference Transcription and Chromatin
  • Place of Presentation: Heidelberg, Germany
  • Year and Date: 2010-08-29
• [Presentation] リン酸化による MafA の転写活性化能および新規の活性の制御機構の解明 (2010)
  • Author(s): 金井賢一
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪
  • Year and Date: 2010-05-20