Novel signaling pathway in Patched1.
| Project/Area Number |
23657135
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cell biology
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YOKOTA Naoto 首都大学東京, 大学院理工学研究科, 助教 (40610564)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | Patched1 / GLI / ヘッジホッグ / ユビキチン / プロテアソーム / 蛋白質品質管理 |
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| Research Abstract |
Patched 1 (Ptc1) is a polytopic receptor protein that is essential for growth and differentiation. Its extracellular domains accept its ligand, Sonic Hedgehog, while the function of its C-terminal intracellular domain is largely obscure. In this study, we stably expressed human Ptc1 protein in HeLa cells and found that it is subjected to proteolytic cleavage at the C-terminus, resulting in the generation of soluble C-terminal fragments. These fragments accumulated in the nucleus, while the N-terminal region of Ptc1 remained in the cytoplasmic membrane fractions. Using an anti-Ptc1 C-terminal domain antibody, we provide conclusive evidence that C-terminal fragments of endogenous Ptc1 accumulate in the nucleus of C3H10T1/2 cells. Similar nuclear accumulation of endogenous C-terminal fragments was observed not only in C3H10T1/2 cells but also in mouse embryonic primary cells. Importantly, the C-terminal fragments of Ptc1 modulate transcriptional activity of Gli1. Although Ptc1 protein was originally thought to be restricted to cell membrane fractions, our findings suggest that its C-terminal fragments can function as an alternative signal transducer that is directly transported to the cell nucleus.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] A novel signaling pathway mediated by the nuclear targeting of C-terminal fragments of mammalian Patched 12011
Author(s)
Kagawa, H., Shino, Y., Kobayashi, D., Demizu, S., Shimada. M., Ariga, H. and Kawahara, H
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Journal Title
PLoS ONE
Volume: 6
Issue: 4
Pages: e18638-e18638
DOI
Related Report
Peer Reviewed
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