Molecular mechanism to dictate RdRP activity of TERT

• Project/Area Number: 15K14482
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: National Cancer Center Japan
• Principal Investigator: Masutomi Kenkichi 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20450570)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: テロメラーゼ / TERT / リン酸化 / RNA依存性RNAポリメラーゼ / 酵素の調節 / タンパク質リン酸化

Outline of Final Research Achievements

TERT has two distinct polymerase activities. One is reverse transcriptase activity and another is RNA dependent RNA polymerase activity. We identified several phosphorylation sites of hTERT by mass spectrometry analysis. We generated polyclonal antibodies against phospho-specific hTERT. Using the antibodies, we identified a phosphprylation site specifically dictates for RdRP activity. Moreover, we found several candidates of upstream kinase by using kinase inhibitors and siRNAs against kinases.