Functional analysis of carboxy-terminal peptide signaling of pro-amphiregulin and pro-epiregulin
Project/Area Number |
20390082
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General medical chemistry
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Research Institution | Ehime University |
Principal Investigator |
HIGASHIYAMA Shigeki Ehime University, プロテオ医学研究センター, 教授 (60202272)
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Co-Investigator(Renkei-kenkyūsha) |
FUKUDA SHINJI 愛媛大学, 大学院・医学系研究科, 助教 (70398238)
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Project Period (FY) |
2008 – 2010
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Project Status |
Completed (Fiscal Year 2010)
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Budget Amount *help |
¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2009: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
|
Keywords | amphiregulin / epiregulin / ectodomain shedding / EGFファミリー / CTF / 膜型増殖因子 / エンドサイトーシス / レトログレード小胞輸送 / 核膜移行 / shedding / repressor |
Research Abstract |
Amphiregulin (AREG) and epiregulin (EREG), members of the EGF family, are synthesized as type I transmembrane protein precursors (proAREG and proEREG) and expressed on the cell surface. Shedding of proAREG and proEREG yield transmembrane-cytoplasmic fragments (AREGF-CTF and EREG-CTF), as well as soluble forms AREG and EREG. Here we demonstrated that the ectodomain shedding stimuli triggered endocytosis of both their CTFs and un-shed forms. They translocated from the plasma membrane to the nuclear membrane via retrograde membrane trafficking. Nuclear envelope localization of proAREG involves truncation of the C-terminus, which subsequently activates the ER-retrieval signal. The truncated form of proAREG interacts with A-type lamin and is retained at the inner nuclear membrane. Heterochromatin formation is then induced and global transcription is transiently suppressed. This study gives new insight into epigenetic chromatin organization in mammalian cells : a plasma-membrane-anchored growth factor is targeted to the inner nuclear membrane where it participates in dynamic chromatin organization and control of transcription.
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells.2010
Author(s)
Ebi M, Kataoka H, Shimura T, Kubota E, Hirata Y, Mizushima T, Mizoshita T, Tanaka M, Mabuchi M, Tsukamoto H, Tanida S, Kamiya T, Higashiyama S, Joh T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 402
Pages: 449-454
Related Report
Peer Reviewed
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[Journal Article] Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice2009
Author(s)
Oyagi A, Oida Y, Kakefuda K, Shimarawa M, Shioda N, Moriguchi S, Kitaichi K, Nanba D, Yamaguchi K, Furuta Y, Fukunaga K, Higashiyama S, Hara H
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Related Report
Peer Reviewed
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[Journal Article] BCL6 degradation caused by the interaction with the C-terminus of pro-HB-EGF induces cyclin D2 expression in gastric cansers2009
Author(s)
Hirata Y, Ogasawara N, Sasaki M, Mizushima T, Shimura T, Mizoshita T, Mori Y, Kubota E, Wada T, Tanida S, Kataoka H, Kamiya T, Higashiyama S, Joh T
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Journal Title
BrJCancer 100
Pages: 1320-1329
Related Report
Peer Reviewed
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