Establishment of a platform for development of tumor treatment seeds targeting a novel transcription elongation regulator Med26

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19578
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology and related fields
• Research Institution: Yokohama City University
• Principal Investigator: Takahashi Hidehisa 横浜市立大学, 医学研究科, 教授 (30423544)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 遺伝子発現制御 / 転写 / 腫瘍性疾患

Outline of Final Research Achievements

The purpose of this study is to identify compounds that inhibit the binding between Med26 and SEC, and to develop anti-neoplastic drugs that suppress the growth of cancer cells and acute leukemia cells. Med26 binds SEC through its N-terminal domain (NTD) and promotes the expression of tumor-associated genes.
In this study, we found that GAL4-Med26-NTD, in which the DNA binding domain of the yeast transcription factor GAL4 was fused to the NTD of Med26, exerts inrinsic transcription activity in cells by binding to SEC. Therefore, in this study, we generated cell line that stably expresses GAL4-Med26-NTD and detects de novo transcription.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

転写伸長因子P-TEFbをリクルートするBRD4の阻害剤JQ1は、強い抗腫瘍効果を発揮することから世界的に注目されている。Med26の阻害剤は、SEC（2つの転写伸長因子P-TEFbとELL/EAF）のリクルートを阻害することから、得られる可能性のある化合物はJQ1よりも強い抗腫瘍効果を発揮することが期待される。