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

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• 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 / タンパク質リン酸化 / 遺伝子発現調節 / 糖尿病 / 細胞内局在 / タンパク質 / リン酸化 / 遺伝子発現制御 / インスリン / 転写調節因子複合体

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 beta-cell-enriched transcription factors, MafA, Pdx1, and beta2, and activates insulin gene transcription (2011)
  • Author(s): Song-iee Han, Kunio Yasuda, Kohsuke Kataoka
  • Journal Title: J Biol Chem Volume: 286(12) Issue: 12 Pages: 10449-56
  • DOI: 10.1074/jbc.m110.209510
  • Peer Reviewed
• [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 Issue: 1 Pages: 119-127
  • DOI: 10.1530/jme-11-0044
  • Peer Reviewed
• [Journal Article] MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development (2011)
  • Author(s): Kamitani-Kawamoto A, Hamada M, Moriguchi T, Miyai M, Hitoshi S, Ikenaka K, Hosoya T, Hotta Y, Takahashi S, Kataoka K
  • Journal Title: J Bone Mineral Res Volume: 26 Issue: 10 Pages: 2463-2472
  • DOI: 10.1002/jbmr.458
  • Peer Reviewed
• [Journal Article] ATF2 interacts with beta-cell-enriched transcription factors, MafA, Pdx1, and Beta2, and activates insulin gene transcription. (2011)
  • Author(s): S.-i.Han
  • Journal Title: Journal of Biological Chemistry Volume: 286 Pages: 10449-10456
  • Peer Reviewed
• [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
• [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
• [Journal Article] SUMOylation negatively regulates transcriptional and oncogenic activities of MafA. (2010)
  • Author(s): K.Kanai
  • Journal Title: Genes to Cells. Volume: 15 Pages: 971-982
  • Peer Reviewed
• [Journal Article] Insulin transactivator MafA regulates intra-thymic expression of insulin and affects susceptibility to type I diabetes. (2010)
  • Author(s): S.Noso
  • Journal Title: Diabetes Volume: 59 Pages: 2579-2587
  • Peer Reviewed
• [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] Phosphorylations regulate transcriptional and non-transcriptional activity of MafA in oncogenic transformation. (2010)
  • Author(s): K.Kanai
  • Organizer: 9^<th> EMBL 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
• [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