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It has been suggested that Helicobacter pylori(H. pylori) infections can promote the development and progression of gastric cancer through the modulation of cell cycle regulators such as p27Kip1 and Skp2. p27Kip1 is a cyclin-dependent kinase (CDK) inhibitor that blocks the G1/S transition necessary for cell cycle progression. Skp2 is a component of the ubiquitin ligase complex called SCFSkp2(SKP1-Cullin-F-box), which specifically binds and promotes the degradation of p27Kip1. A low level of p27Kip1 and a high level of Skp2 have been reported in many types of cancers, including gastric cancer. In addition,a decrease in p27Kip1 has been reported in H. pylori-infected specimens. However, data on Skp2 in H. pylori infections are limited. This study examines the changes in the status of Skp2 in H. pylori-infected gastric epithelial AGS cells. For this, we stimulated AGS cells with H. pylori(NCTC 11637) at the ratio of 300:1(bacterium:cell) for 6 hours. The results of an immunoprecipitation analysis, followed by a western blot, indicate that the interaction between Skp2 and 14-3-3 was elevated 3 hours after the H. pylori treatment. In addition, there was an increase in cytoplasmic Skp2 after 3 hours, whereas there was no change in the nuclear level. Since it has been reported that interaction with 14-3-3 and the subsequent cytoplasmic translocation of Skp2 can increase its protein stability, increases in the interaction with 14-3-3 and the cytoplasmic Skp2 after the H. pylori treatment can increase the level of Skp2 in AGS cells. This phenomenon may explain,at least to some extent, the mechanism underlying the relationship between H. pylori infections and gastric carcinogenesis.
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참고문헌 (24건) : 자료제공( 네이버학술정보 )
| 번호 | 참고문헌 | 국회도서관 소장유무 |
|---|---|---|
| 1 | 보건복지부 암등록통계(통계청 지정통계 11744호) | 미소장 |
| 2 | Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells.  |
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| 3 | Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase. |
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| 4 | p27 Protein and cancers of the gastrointestinal tract and liver: an overview. |
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| 5 | Helicobacter pylori Increases Proteasome-mediated Degradation of p27^k^i^p^1 in Gastric Epithelial Cells |
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| 6 | Prognostic significance of p21WAF1/CIP1, p27Kip1, p53 and E-cadherin expression in gastric cancer. |
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| 7 | Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1. |
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| 8 | Kim SS, Meitner P, Konkin TA, Cho YS, Resnick MB, Moss SF. 2006. Altered expression of Skp2, c-Myc and p27 proteinsbut not mRNA after H. pylori eradication in chronicgastritis. Mod Pathol 19:49-58 | 미소장 |
| 9 | Gastric cancer and Helicobacter pylori infection |
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| 10 | Role of the F-box Protein Skp2 in Lymphomagenesis |
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| 11 | Laurèn P. 1965. Two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand 64:31-49 | 미소장 |
| 12 | NF-kB p65 regulates nuclear translocation of Ku70 via degradation of heat shock cognate protein 70 in pancreatic acinar AR42J cells |
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| 13 | Lin H, Wang G, Chen Z, Teruya-Feldstein J, Pandolfi PP. 2009. Phosphorylation-dependent regulation cytosolic localization andoncogenic function of Skp2 by Akt/PKB. Nat Cell Biol 11:420-432 | 미소장 |
| 14 | Localization of the CDKN4/p27Kip1 gene to human chromosome 12p12.3. |
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| 15 | Frequent loss of expression of the cyclin-dependent kinase inhibitor p27 in epithelial ovarian cancer. |
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| 16 | Immunohistochemical Study of p27Kip1 Expression in Gastric Adenomas and Early Gastric Carcinomas: Analysis of 65 Cases | 소장 |
| 17 | Peek RM Jr, Blaser MJ. 2002. Helicobacter pylori and gastrointestinaltract adenocarcinomas. Nat Rev Cancer 2:28-37 | 미소장 |
| 18 | p27Kip1: Regulation and Function of a Haploinsufficient Tumor Suppressor and Its Misregulation in Cancer |
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| 19 | Regulation of Nuclear Transport: Central Role in Development and Transformation? |
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| 20 | Chronic Helicobacter pylori Infection Induces an Apoptosis-Resistant Phenotype Associated with Decreased Expression of p27 kip1 |
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| 21 | Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex |
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| 22 | The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity |
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| 23 | How do 14-3-3 proteins work? – Gatekeeper phosphorylation and the molecular anvil hypothesis |
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| 24 | Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia. |
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