Analysis of the molecular interaction between KRAP and IP3R and its application for drug discovery

• Project/Area Number: 24710265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Kyoto Prefectural University of Medicine (2013-2014); Fukuoka University (2012)
• Principal Investigator: FUJIMOTO Takahiro 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10446114)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 分子間相互作用 / 分子標的 / カルシウムイオンシグナル / 癌 / リンパ球 / 翻訳後修飾 / リン酸化 / 化合物 / バイオプローブ

Outline of Final Research Achievements

Through the analysis of the molecular interaction between KRAP and IP3Rs, KRAP homolog gene was identified. KRAP homolog protein was specifically expressed in T- and B-lymphocytes and was found to interact with IP3Rs. KRAP homolog protein was localized around microdomain between ER and mitochondrial membranes, and appeared to regulate calcium ion flow from ER to mitochondria. It was worthy to note that both KRAP homolog and KRAP were phosphorylated upon extracellular calcium ion influx in lymphocytes and cancer cells, respectively. In this study, chemical screening to explore candidate of cancer drug targeting to KRAP-IP3R interaction was failed. However, elucidation of the molecular mechanisms underlying posttranslational modification of KRAP family proteins may provide a novel strategy for cancer theraphy.

Research Products

• [Journal Article] Tespa1 protein is phosphorylated in response to store-operated calcium entry. (2013)
  • Author(s): Fujimoto T, Matsuzaki H, Tanaka M, Shirasawa S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 434 Pages: 162-165
  • Peer Reviewed
• [Journal Article] Tespa1 is a novel component of mitochondria-associated endoplasmic reticulum membranes and affects mitochondrial calcium flux. (2013)
  • Author(s): Matsuzaki H, Fujimoto T, Tanaka M, Shirasawa S.
  • Journal Title: Biochem Bio- phys Res Commun Volume: 433(3) Issue: 3 Pages: 322-326
  • DOI: 10.1016/j.bbrc.2013.02.099
  • Peer Reviewed
• [Journal Article] Tespa1 is a novel inositol 1,4,5-trisphosphate receptor binding protein in T and B lymphocytes. (2012)
  • Author(s): Matsuzaki H, Fujimoto T, Ota T, Ogawa M, Tsunoda T, Doi K, Hamabashiri M, Tanaka M, Shirasawa S
  • Journal Title: FEBS Open Bio Volume: 2 Pages: 255-259
  • Peer Reviewed
• [Journal Article] Identification of KRAP-expressing cells and the functional relevance of KRAP to the subcellular localization of IP3R in the stomach and kidney. (2012)
  • Author(s): Fujimoto T.
  • Journal Title: Int J Mol Med. Volume: 30(6) Issue: 6 Pages: 1287-1293
  • DOI: 10.3892/ijmm.2012.1126
  • Peer Reviewed
• [Presentation] 癌・代謝関連遺伝子KRAPの細胞内カルシウムイオン制御機構に関する研究 (2012)
  • Author(s): 藤本崇宏、白澤専二
  • Organizer: 日本人類遺伝学会第57回大会
  • Place of Presentation: 東京