Regulatory mechanisms of the leukemia-associated transcription factor, RUNX1/AML1, through the post-translational modifications.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: TSUKASA Okuda 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
• Co-Investigator(Kenkyū-buntansha): SAKAKURA Chouhei 京都府立医科大学, 大学院医学研究科, 准教授 (10285257)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 白血病 / 造血幹細胞 / リンパ球 / 転写因子 / 翻訳後修飾 / RUNX1 / AML1 / マウスモデル

Outline of Final Research Achievements

RUNX1 is a leukemia-associated transcription factor that functions in hematopoietic development, proliferation, and differentiation. In this study, biological significance of the methylation of two arginine residues (R206/210) was analyzed. To this end, we made mutant RUNX1 in which both R206 and R210 were substituted to lysine (K) that cannot be methylated by the responsible enzyme. Although this non-methylable mutant protein showed somewhat reduced trans-activating activity in vitro, it still retained the biological ability to rescue the hematopoietic defect found in Runx1-deficient murine ES cells. In addition, engineered mice that homozygously carry these R-to-K mutations showed no obvious defects in myeloid, meg/platelet, or B-cell lineages. However, the mutant mice showed reduced number for CD4-single positive T-cells for peripheral blood and spleen. Thus, our results revealed that methylation of Runx1 is important for homeostasis of the peripheral CD4+ lymphocyte population.

Free Research Field

生化学　分子生物学　腫瘍学