Understanding mechanisms that regulate Runx complex function through C-terminus structures

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04090
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Taniuchi Ichiro 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (20284573)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫細胞 / 細胞分化 / 転写因子 / Runx

Outline of Final Research Achievements

unx/Cbfb transcription factor complexes are known to play essential roles in regulating development of multiple types of cells. Our preliminary works showed that C-terminal end sequences of Runx and Cbfb2 are important for the function of Runx/Cbfb complexes. In this study, we focuses on the last Y residue in the Runx3 protein and replaced the Y with W, F or E residue. Analyses of these mutant lines suggested that the Y residue might be phosphorylated and this post-translational modification is quite essential for regulating the function of Runx protein.
As for the functional characterization of Cbfb2-specific C-terminal amino-acid sequences, proteomics approach and analyses of a new mutant strain lacking the above Cbfb2-specific C-terminal sequences failed to find Cbfb2-specific interacting partners and function, respectively. These finding suggest that RNA splicing at the Cbfb locus might contribute to regulate total amount of Cbfb protein.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果からRunxタンパクの最後のY残基がRunxタンパクの機能、特に外部刺激に応答した遺伝子発現抑制と細胞周期制御に重要であることを強く示唆する結果を得た。免疫学領域では抗原受容体刺激後のリンパ球の選択機構の分子ネカニズムの解明は大きな課題であり、今回の成果はこの問題の解明に繋がる成果であると考えられる。