The function of RNF43 in tumorigenesis and maintaining homeostasis
| Project/Area Number |
16K07105
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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 |
Tumor biology
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 多段階発がん / Wnt / p53 / RNF43 / Ras / リン酸化 / ユビキチン化 / 発がん / 形態形成 / 恒常性維持 / 幹細胞 / Fzd / Dvl / がん / 突然変異 / 恒常性 |
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| Outline of Final Research Achievements |
We show in this research that;
1, CK1 phosphorylates RNF43 on multiple serines. 2, Phosphorylation activates ubiquitinating function of RNF43. 3, Mutation of RNF43 in these serines induces the excess of Wnt signaling. 4, Such mutations do not change the function of RNF43 in suppression of p53-dependent cellular reactions.
These results suggest that mutations in serine on RNF43 act concurrently in the first step: Wnt activation and in the 3rd step: p53 inactivation. Furthermore, we propose a new model of tumorigenesis: two mutations, in RNF43 and Ras, is sufficient for the onset of tumor.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではRNF43によるWntシグナルとp53シグナルの調節機構が恒常性維持にどのような役割を果たしているか検討した。さらにその調節メカニズムの破綻によりどのように発がんに関与しているかを明らかにした。その結果、発がんに必要とされる3つのステップの中で2つが単一の遺伝子変異によって同時に達成されてしまう可能性を示唆した。この結果はこれまでのがん研究を更に発展させる新たな概念を創出したと考えられる。また今後のがん治療研究への応用においても大きな意義を持つと考えられる。
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Report
(5 results)
Research Products
(23 results)
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[Journal Article] The role of Mediator and Little Elongation Complex in transcription termination2020
Author(s)
Takahashi H, Ranjan A, Chen S, Suzuki H, Shibata M, Hirose T, Hirose H, Sasaki K, Abe R, Chen K, He Y, Zhang Y, Takigawa I, Tsukiyama T, Watanabe M, Fujii S, Iida M, Yamamoto J, Yamaguchi Y, Suzuki Y, Matsumoto M, Nakayama KI, Washburn P, Saraf A, Florens L, Sato S, Tomomori-Sato C, Conaway RC, Conaway JW, Hatakeyama S
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Journal Title
Nature Communications
Volume: 11
Issue: 1
Pages: 1-20
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Type XVII collagen coordinates proliferation in the interfollicular epidermis.2017
Author(s)
Watanabe M, Natsuga K, Nishie W, Kobayashi Y, Donati G, Suzuk Si, Fujimura Y, Tsukiyama T, Ujiie H, Shinkuma S, Nakamura H, Murakami M, Ozaki M, Nagayama M, Watt F and Shimizu H
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Journal Title
eLife
Volume: 6:e26635
Pages: 1-24
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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