Identification of a novel binding partner of an oncogenenic protein MYC

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16791
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Miyamoto Ryo 国立研究開発法人国立がん研究センター, 研究所, 外来研究員 (40770863)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: MYC / タンパク質相互作用 / 免疫沈降 / 白血病

Outline of Final Research Achievements

MYC is a transcriptional factor to control a large number of genes associated with cellular metabolism and proliferation. MYC is deregulated in the majority of human cancers, and its overexpression is often correlated with poor prognosis. Although the blockade of MYC is an attractive approach to abrogate the MYC-overexpressed cancers, direct targeting of MYC has been a challenge due to its undruggable protein structure. This study utilized a unique ChIP method to identify a novel MYC binding partner. MYC associated with the binding protein at its multiple protein portions. knockout of the identified protein significantly reduced clonogenic potential of MYC in a colony formation assay. This study provides a potential alternative approach to control MYC by targeting its binding partner.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

MYCはがんの発生・悪性化に関わる重要な因子であるが、薬剤を用いたMYC機能の制御は困難とみられている。別の制御戦略を探るため、本研究では独自の手法によりMYCと結合するタンパク質を解析し、未報告の結合タンパク質を特定した。MYCタンパク質を用いてMYC側の結合部位を明らかにし、かつMYC過剰発現細胞を用いて結合タンパク質の減少が細胞増殖を抑えることを見出した。本研究は特定した新規のMYC結合タンパク質がMYC制御に向けた新たな創薬対象になることを示す。