The Role in APC stability control mechanism by EDD
| Project/Area Number |
18591486
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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 |
Digestive surgery
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
OTSUBO Takehito St.Marianna University School of Medicine, Department of Surgery, Professor (50398971)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Tomohiko St. Marianna University School of Medicine, Department of Surgery, Associate Professor (60233136)
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| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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|---|
| Keywords | tumor suppressor / hyd / EDD / 家族性大腸ポリポーシス / colon cancer / APC |
|---|
| Research Abstract |
Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a key player in the Wnt signaling pathway. While the role of APC in inhibition of β-catenin/LEF1-dependent activation of transformation-inducing genes has been intensively studied and well established, regulation of APC expression at the protein level is only partially understood. Here we report that APC is up-regulated by EDD, the mammalian orthologue of Drosophila melanogaster hyperplastic discs gene (hyd) that is considered to be a putative tumor suppressor. Screening of APC immunocomplexes by mass spectrometry identified EDD as a putative APC-interacting protein. Exogenously expressed and endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Overexpression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of □-catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein level without altering its mRNA level, causing enhanced protein expression of □-catenin. Thus through protein-protein interaction, EDD stabilizes APC and up-regulates APC's function to inhibit □-catenin, suggesting that EDD could act as a colorectal tumor suppressor.
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Report
(3 results)
Research Products
(40 results)
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Author(s)
Shimo A, Tanikawa C, Nishidate T, Lin ML, Matsuda K, Park JH, Ueki T, Ohta T, Hirata K, Fukuda M, Nakamura Y, Katagiri T.
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Journal Title
Cancer Sci. 99(1)
Pages: 62-70
NAID
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Journal of Surgical Research 145
Pages: 49-56
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[Journal Article] Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase'Synoviolin'.2007
Author(s)
Yamasaki S, Yagishita N, Sasaki T, Nakazawa M, Kato Y, Yamadera T, Bae E, Toriyama S, Ikeda R, Zhang L, Fujitani K, Yoo E, Tsuchimochi K, Ohta T, Araya N, Fujita H, Aratani S, Eguchi K, Komiya S, Maruyama I, Higashi N, Sato M, Senoo H, Ochi T, Yokoyama S, Amano T, Kim J, Gay S, Fukamizu A, Nishioka K, Tanaka K, Nakajima T.
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[Journal Article] Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver.2007
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Journal Title
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Pages: 247-255
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