p115RhoGEF promote differentiation of human acute leukemic cells

• Project/Area Number: 24591540
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: Suzuki Nobuchika 東京大学, 先端科学技術研究センター, 助教 (90247007)
• Co-Investigator(Kenkyū-buntansha): Kawamura Takeshi 東京大学, アイソトープ総合センター, 准教授 (70306835) ; Kozasa Tohru 東京大学, 先端科学技術研究センター, 特任教授 (70202059)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細胞分化 / RH-RhoGEF / 核膜 / Rho活性化因子 / 白血病 / 核エンベロープ / リン酸化修飾 / 白血病細胞 / 分化 / 核移行

Outline of Final Research Achievements

Here we demonstrate that p115RhoGEF, a guanine nucleotide exchange factor for Rho, directly interacts with a protein at the nuclear periphery to organize the nuclear envelope and transcriptional regulators and thus promote differentiation of human leukaemic HL60 cells. Translocation of p115RhoGEF from the cytoplasm to the nucleus, in response to all-trans retinoic acid is initiated upon its phosphorylation on the specific phosphorylation site. This novel p115RhoGEF signal into the nucleus differentiates leukaemic cells, accompanied by the canonical p115RhoGEF-RhoA-actin organization at the plasma membrane.

Research Products

• [Int'l Joint Research] Thomas Jefferson University(米国)
• [Journal Article] Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1 (2015)
  • Author(s): Helms, M. C. Grabocka, E. Martz, M. K. Fischer, C. C. Suzuki, N. Wedegaertner, P. B.
  • Journal Title: Cell Signal Volume: 28 Issue: 1 Pages: 43-52
  • DOI: 10.1016/j.cellsig.2015.10.004
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Gα13/PDZ-RhoGEF/RhoA signaling is essential for gastrin-releasing peptide receptor-mediated colon cancer cell migration. (2014)
  • Author(s): Patel M, Kawano T, Suzuki N, Hamakubo T, Karginov AV, Kozasa T.
  • Journal Title: Mol Pharmacol Volume: 86 Issue: 3 Pages: 252-262
  • DOI: 10.1124/mol.114.093914
  • Peer Reviewed / Open Access
• [Journal Article] G protein-dependent basal and evoked endothelial cell vWF secretion. (2014)
  • Author(s): Rusu L, Andreeva A, Visintine DJ, Kim K, Vogel SM, Stojanovic-Terpo A, Chernaya O, Liu G, Bakhshi FR, Haberichter SL, Iwanari H, Kusano-Arai O, Suzuki N, Hamakubo T, Kozasa T, Cho J, Du X, Minshall RD.
  • Journal Title: Blood Volume: 123 Issue: 3 Pages: 442-450
  • DOI: 10.1182/blood-2013-03-489351
  • Peer Reviewed
• [Journal Article] Modification of p115RhoGEF Ser(330) regulates its RhoGEF activity. (2013)
  • Author(s): CHOW, C. R., SUZUKI, N., KAWAMURA, T., HAMAKUBO, T. & KOZASA, T.
  • Journal Title: Cell Signal Volume: 25 Issue: 11 Pages: 2085-92
  • DOI: 10.1016/j.cellsig.2013.06.012
  • Peer Reviewed
• [Journal Article] GPCRシグナルの動的作用機構の解明―タンパク質表面のインターフェースに注目した、新たな熱力学的解析 (2013)
  • Author(s): 鈴木信周、小笹徹。
  • Journal Title: 実験医学 Volume: 31 Pages: 399-405
• [Presentation] p115RH-RhoGEF targets lamin B to promote the differentiation of human leukemic cells (2014)
  • Author(s): SUZUKI, N., KAWAMURA, T., HAJICEK, T, HAMAKUBO, T. & KOZASA, T
  • Organizer: Gordon Research Conference
  • Place of Presentation: University of New England, Biddeford, ME, USA
  • Year and Date: 2014-06-15 – 2014-06-20
• [Presentation] Cdk1-dependent phosphorylation of leukemia-associated RhoGEF during mitosis (2014)
  • Author(s): M.C. Helms, E. Grabocka, M.K. Martz, N. Suzuki and P.B. Wedegaertner
  • Organizer: Experimental Biology
  • Place of Presentation: San Diego Convention center, USA
  • Year and Date: 2014-04-28
• [Presentation] The role of p115RhoGEF during differentiation of human myeloid HL60 leukemia cells (2012)
  • Author(s): Nobuchika Suzuki, Takeshi Kawamura, Hiroko Iwanari, Takao Hamakubo, Tohru Kozasa
  • Organizer: Gordon Research Conference
  • Place of Presentation: Univ of New England, USA
• [Remarks] 東京大学先端科学技術研究センター システム生物医学ラボラトリー
  • URL: http://www.lsbm.org