| Project/Area Number |
18K09244
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Mori Seiichiro 国立感染症研究所, 病原体ゲノム解析研究センター, 主任研究官 (80342898)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | パピローマウイルス / 遺伝子発現 / 転写因子 / 転写共役因子 / 子宮頸がん / ペプチド薬 |
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| Outline of Final Research Achievements |
The TEAD family of transcription factors requires associating cofactors to induce gene expression. TEAD1 is known to activate the early promoter of human papillomavirus (HPV), but the precise mechanisms of TEAD1-mediated transactivation of the HPV promoter, including its relevant cofactors, remain unexplored. In this study, we revealed that VGLL1, a TEAD-interacting cofactor, contributes to HPV early gene expression. Knockdown of VGLL1 and/or TEAD1 led to a decrease in viral early gene expression in human cervical keratinocytes and cervical cancer cell lines. We identified 11 TEAD1 target sites in the HPV16 long control region (LCR). VGLL1 bound to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. These results suggest that multiple VGLL1/TEAD1 complexes are recruited to the LCR to support the efficient transcription of HPV early genes.
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| Academic Significance and Societal Importance of the Research Achievements |
HPVの遺伝子発現に関わる多くの宿主転写因子が報告されているが、転写共役因子についてはほとんど知られていない。本研究で、転写共役因子VGLL1が、転写因子TEAD1を介してHPVゲノムの転写調節領域に結合し、転写を活性化することが明らかとなった。TEAD1が広範な細胞種で発現しているのに対し、VGLL1は主に上皮細胞で発現していることから、VGLL1はHPVの上皮細胞への指向性に関わる重要な宿主因子と推測される。また、shRNAを用いてVGLL1をノックダウンすると子宮頸がん細胞の増殖が抑制されたことから、VGLL1は子宮頸がん治療の標的分子となり得る。
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