| Project/Area Number |
13470033
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
AKIYAMA Testu The University of Tokyo, Institute of Molecular and Cellular Biosciences, Professor, 分子細胞生物学研究所, 教授 (70150745)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
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| Keywords | Tumor suppressor / Peutz-Jeghers syndrome / LKB1 / STK11 / Hamartomatous polyps / Serine-threonine kinase / Peutz-Jeghers症候群 / LKB1AP / 好発癌性疾患 |
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| Research Abstract |
Peutz-Jeghers syndrome is an autosomal dominant disease. Early manifestations of Peuts-Jegehers syndrome include melanocytic macules of the lips and multiple hamartomatous polyps in the gastrointestinal tract. Later in life, Peuts-Jeghers syndrome patients have a dramatically increased incidence of cancers in a wide variety of tissues. We investigated the mechanism and function of LKB1/STK11, a Ser/Thr kinase mutated in Peutz-Jehgers syndrome, and made the following findings. 1) We performed a yeast two-hybrid screen using LKB/STK11 as bait, and identified the LMO family of transcription factors as partners for LKB1/STK11. 2) The LMO family of transcription factors interacts with GATA and activates its activity. 3) In cooperation with p53, the LMO family of transcription factors activates the expression of CDK inhibitor p21. Ldb1 and GATA6 were also found to participate in the LMO family-mediated transactivation of p21. 4) Overexpression of LKB1/STK11 in Hela cells as well as in G361 cells resulted in the G1 arrest of the cell cycle. 5) So far we have not succeeded to identify substrate proteins for phosphorylation by LKB1/STK11.
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