Function of NANOG as an inhibition for free c-MYC-dependent apoptosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K15604
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Saitama Medical University
• Principal Investigator: Hirasaki Masataka 埼玉医科大学, 医学部, 助教 (10522154)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ES細胞

Outline of Final Research Achievements

In 2011, our lab reported that extinction of Max gene expression in ES cells provoke cell death. Further studies revealed that the MAX-unbound c-MYC in Max-deficient ES cells is responsible factor for the apoptosis exhibited by these cells, and that NANOG functions as a suppressor of apoptosis induction by binding to free c-MYC. NANOG functions to activate the NuRD complex, and MBD3, a component of NuRD, has been reported to bind to c-MYC. Therefore, we examined whether forced expression of MBD3 suppressed the apoptosis exhibited by Max-deficient ES cells and found that apoptosis was suppressed by forced expression of MBD3. In addition, DNA microarray analysis was performed to determine what kind of gene groups are expressed by the forced expression of MBD3.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

MYCタンパク質は、腫瘍化の要因として考えられている一方、古くからMycの強制発現は、アポトーシスを引き起こすと言う、相反する現象にも関与している事が知られていた。本研究はES細胞における、MYCタンパク質によるアポトーシス誘導という、今までにあまり着目されてこなかった研究項目を中心課題に据えた研究ではあったが、c-MYCに関して全く新しい分子指標を見出すことに繋がったと考えている。この得られた知見はES・iPS細胞の特性の根幹をなす『分化多能性・自己増殖性』の理解につながり、しいてはES・iPS細胞を用いた再生医療の安全性の向上につながる事を期待する。