S100Cタンパク質を介した新規細胞増殖抑制機構の解明

阐明S100C蛋白介导的新型细胞生长抑制机制

• 批准号: 17790150
• 负责人: 阪口 政清
• 金额: $ 2.11万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17790150/
• 关键词: S100C; A11; Annexin I; Phospholipase A2; 表皮角化細胞; 増殖; アラキドン酸; Ca; TGFβ; Smad; NFAT; Sp1; KLF16; ヒト表皮角化細胞

S100C/A11の新たな機能を探る目的で、相互作用のあるタンパク質を検索した。S100C/A11はAnnexin Iに結合するという報告があり、Annexin IはPhospholipase A2(PLA2)に結合しその活性を阻害することを介してアラキドン酸カスケードの制御に関与する。そこで、S100C/A11がAnnexin Iとの結合を介してアラキドン酸カスケードに作用するとの作業仮説の下に、今回検討を行った。その結果、S100C/A11は確かにAnnexin Iに結合し、この複合体形成は試験管内でAnnexin IとPLA2との結合を大幅に増強することがわかった。また、S100C/A11-Annexin I-cPLA2の細胞内での結合に関しても免疫沈降法により確認することができた。さらに、TGFβや高Caで処理するとS100C/A11はリン酸化を受けるが、そのことがこのタンパク質相互作用にどのように影響するかを検討したところ、S100C/A11のリン酸化修飾はこの結合に影響を及ぼさないが、CaのS100C/A11への結合がそのタンパク質問相互作用に重要であることが明らかとなった。ヒト表皮由来細胞の増殖はPLA2(中でもcytosolic PLA2;cPLA2)活性に依存していることが周知である。そこで、S100C/A11の機能状態とその結果としてのS100C/A11-Annexin I複合体形成がcPLA2活性にどのように影響するかを検討した。細胞内遊離アラキドン酸の定量により解析したところ、細胞内cPLA2活性はS100C/A11-Annexin I複合体により著しく抑制されることが明らかとなった。また、表皮角化細胞の増殖がcPLA2活性に依存していることが確認できた。以上、Annexin IがS100C/A11への結合を介してPhospholipase A2(PLA2)活性を効率よく抑制し、細胞増殖を制御する新規機構を明らかにすることができた(投稿準備中)。

The new mechanism of S100C/A11 can explore the purpose and the interaction between each other. The combination of S100C/A11 Annexin I and Annexin I Phospholipase A2 (PLA2) is effective in the control and control of health problems. This is the first time that the operation has been completed. This time, the operation will be completed. This time, the operation will be completed in the first half of the year. This time, the operation will be completed. This time, the operation will be completed. The results were confirmed by S100C/A11, the combination of Annexin I was confirmed by S100C/A11, and the complex was formed by the combination of Annexin I and DNA in the tube. The method of immunoprecipitation was combined with the combination of S100C/A11-Annexin I-cPLA2 and cytosol to make sure that the mice were infected. The effects of high Ca, TGF β and Ca β on S100C/A11 acidification were studied in detail. The interaction was affected. The effects of the interaction were studied. The effects of acid treatment on the interaction were analyzed. The results showed that the effects of the combination of the effects of the acid treatment on the interaction between the two groups were significant. The origin of the epidermis, the origin of the epidermis, the activity of PLA2 (medium cytosolic PLA2;cPLA2), the activity of the epidermis, the origin of the epidermis, the cells of the epidermis, the activity of cytosolic PLA2;cPLA2. The results showed that the S100C/A11-Annexin I complex formed an active S100C/A11-Annexin complex that affected the activity of cPLA2. The intracellular cPLA2 activity and S100C/A11-Annexin I complex were analyzed by quantitative analysis of intracellular cPLA2 activity and intracellular DNA activity. Epidermis keratosis and epidermal keratosis. CPLA2 activity is dependent on epidermal keratosis. Above, Annexin I S100C/A11 assay combined with the introduction of Phospholipase A2 (PLA2) activity inhibition, cellular colonization and control of the new regulation mechanism is in preparation for submission.

项目成果

Involvement of deterioration in S100C/A11-mediated pathway in resistance of human squamous cancer cell lines to TGFβ-induced growth suppression

• DOI: 10.1007/s00109-007-0180-7
• 发表时间: 2007-05
• 期刊: Journal of Molecular Medicine
• 作者: Hiroyuki Sonegawa;T. Nukui;Dai Li;M. Takaishi;M. Sakaguchi;N. Huh

Bifurcated converging pathways for high Ca^<++>- and TGFb-induced inhibition of growth of normal human keratinocytes

高Ca^<>-和TGFb诱导的正常人角质形成细胞生长抑制的分叉汇聚途径

• 发表时间: 2005
• 期刊: Proceedings of the National Academy of Sciences of the United States of America 102
• 作者: Sakaguchi M;Sonegawa H;Nukui T;Sakaguchi Y;Miyazaki M;Namba M;Huh NH.
• 通讯作者: Huh NH.

Intracellular delivery of proteins into mammalian living cells by polyethylenimine-cationization

• DOI: 10.1263/jbb.99.95
• 发表时间: 2005-02-01
• 期刊: JOURNAL OF BIOSCIENCE AND BIOENGINEERING
• 影响因子: 2.8
• 作者: Futami, J;Kitazoe, M;Yamada, H
• 通讯作者: Yamada, H

Denatured and reversibly cationized p53 readily enters cells and simultaneously folds to the functional protein in the cells

• DOI: 10.1021/bi052642a
• 发表时间: 2006-05-16
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Murata, Hitoshi;Sakaguchi, Masakiyo;Yamada, Hidenori
• 通讯作者: Yamada, Hidenori

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外科前沿

• 发表时间: 2015
• 作者: Sumi S;Yanai G;Yang K-C;Shirouzu Y;有上貴明
• 通讯作者: 有上貴明