| Project/Area Number |
16591645
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAGAWA Shunsuke The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70270874)
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| Co-Investigator(Kenkyū-buntansha) |
YANO Tetsu The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (90251264)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | tumor suppressor / cell polarity / human papillomavirus / E6 oncoprotein / ubiquitin-mediated degradation / ubiquitin protein ligase / cell cycle / growth inhibition / human Scribble / 癌抑制蛋白 / LAP蛋白 / 遺伝子治療 |
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| Research Abstract |
Drosophila tumor suppressor Scribble was identified as an apical-basolateral polarity determinant in epithelia. Human homologue of Drosophila Scribble, human Scribble (hScrib), has been identified as a protein targeted by human papillomavirus E6 for the ubiquitin-mediated degradation depending on E6AP, a cellular ubiquitin-protein ligase. Human Scribble is classified as a LAP protein, having leucine-rich repeats (LRRs) and PDZ domains. We investigated whether hScrib, which is thought to have a role in polarity determination based on the data of its Drosophila homologue, is involved in cell-cycle regulation and proliferation control of epithelia. Transfection of hScrib suppresses cell proliferation by blocking cell-cycle progression from G1 to S phase. We explored functional domain mapping to reveal which domains of hScrib are critical for its cellular proliferation control and localization at the basolateral membrane. We found that LRRs and PDZ domain 1 are indispensable for hScrib to inhibit cell growth by blocking cell-cycle progression and keep its proper localization. These data indicate that basolateral membrane localization of hScrib is closely related to its proliferation control. Our findings suggest the possibility that hScrib is involved in signal transduction to negatively regulate cell proliferation by localizing at basolateral membrane of epithelial cells through LRRs and PDZ domains.
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