RUNX1 as a molecular target for a novel hematopoietic reguation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09487
• 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: OKUDA Tsukasa 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
• Co-Investigator(Kenkyū-buntansha): 吉田 達士 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80315936)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 白血病 / 造血幹細胞 / リンパ球 / 転写因子 / 翻訳後修飾 / RUNX1 / AML1 / TRAIL

Outline of Final Research Achievements

Runt-related transcription factor 1, RUNX1, is a frequent target of leukemia-related gene aberrations. Although a number of the transcriptional target genes have been so far identified, many should still remain to be elucidated. In this project, we identified that tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL) is the novel transcriptional target of RUNX1. TRAIL is a secreted cytokine or a membrane-binding molecule that functions in anti-tumor effects. We found that RUNX1 up-regulated TRAIL promoter activity, detected by the luciferase reporter assay. In this promoter region, some possible RUNX1-binding consensus sequences were found, however, a site-directed mutagenesis revealed that none of them appeared to be responsible for the activation of TRAIL transcription by RUNX1. Further analyses revealed that the proximal region was responsible for this RUNX1 transcription activity, suggesting that RUNX1 regulates TRAIL transcription by a novel molecular mechanism.

Free Research Field

生化学　分子生物学　腫瘍学