Mechanism of TLP as a mediator in p53-p21 pathway
| Project/Area Number |
24570193
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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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| Research Field |
Molecular biology
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| Research Institution | Chiba University |
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Principal Investigator |
Tamura Takaaki 千葉大学, 理学(系)研究科(研究院), 教授 (30112692)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 転写制御因子 / TLP / p53 / TFIIA / TFⅡA / プロモーター / TATA-box / 転写制御 / p21 |
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| Outline of Final Research Achievements |
We first examined the significance of p53 binding of TLP. We found that the p53 binding of TLP prevents p53 binding of MDM2, which destabilizes p53 via ubiquitin-proteasome system. This p53 binding of TLP results in concentration of p53 in the nucleus, which is antagonized by MDM2, and potentiates various p53 downstream genes. We suggest that TLP potentiates p53 both in transcriptional activation and protein stabilization. Second, we examined the significance of TFIIA binding of TLP. We found that the TLP binding results in inhibition of Taspase1-mediated processing of the precursor TFIIA. TLP potentiates transcription of TATA-less promoters but represses TATA promoters. Moreover, mature TFIIA is preferentially used for a preinitiation complex for TATA promoters. These mechanisms can explain why TLP inhibits TATA promoters. TLP may work as a molecular tuner for genomic gene expression. We also found that TFIIA stabilizes TLP, which is degraded by ubiquitin-proteasome system.
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Report
(5 results)
Research Products
(28 results)
