Integrated analyses of biological functions of sugar chains : Glycomics

糖链生物学功能的综合分析：糖组学

• 批准号: 13854010
• 负责人: TANIGUCHI Naoyuki
• 金额: $ 78.71万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13854010/
• 关键词: sugar chain; glycosyltransferase; matriptase; GnT-III; GnT-V; Fut 8; adhesion molecule; growth factor receptor; がん転移; 糖鎖生物学; プロテアーゼ; 発生・分化; グライコミクス; 再生医療; 血管新生; アポトーシス; 硫酸化転移酵素; EGF受容体; がんの転移; βカテニン; 異種移植

To know biological functions of sugar chain by integrated analyses, we have identified target glycoproteins of specific glycosyltransferases as follows.GnT-V catalyses the synthesis of beta 1-6 GlcNAc branching which involves inn tumor metastasis and invasion. In this project, we identified matriptase as a target molecule of GnT-V, which can activate uPA, and HGF. Addition of betal-6 GlcNAc branching on matriptase brought prolonged degradation of these proteins, leading to tumor metastasis in nude mice experiments.Cadherin and integrin are target molecules for GnT-III which involves in the synthesis of bisecting GlcNAc structure. Bisecting GlcNAc inhibit further processing of N-glycan elongation via GnT-V or GnT-IV. In this project, biological functions of sugar chains on integrin and ECM interaction were clarified as a level of purified molecules. Cadherin/beta catenin system is also regulated by GnT-III. Phosphorylation of beta-catenin is suppressed by GnT-III and expression of e-cadherin is controlled by GnT-IIIFut8 involves in core fucosylation on N-glycans. To know physiological meaning of Fut8, we established Fut8 deficient mice. This mouse shows severe growth retardation and 70% of mice die within 3 days after birth. Interestingly, pathological analysis showed emphysema-like lesion in lung of the mice. The mechanism underlying this change is due to dys-regulation of TGF beta-receptor, leading to increases in MMP expression.

为了通过综合分析了解糖链的生物学功能，我们鉴定了以下特异性糖基转移酶的靶糖蛋白：GnT-V催化β 1-6 GlcNAc分支的合成，该分支参与肿瘤的转移和侵袭。在这个项目中，我们鉴定了间质蛋白酶作为GnT-V的靶分子，其可以激活uPA和HGF。在matriptase上添加β 1 -6 GlcNAc分支会延长这些蛋白的降解，导致裸鼠实验中的肿瘤转移。钙粘蛋白和整合素是GnT-III的靶分子，GnT-III参与合成二等分GlcNAc结构。二等分GlcNAc通过GnT-V或GnT-IV抑制N-聚糖延伸的进一步加工。在这个项目中，糖链对整合素和ECM相互作用的生物学功能被阐明为纯化分子的水平。钙粘蛋白/β连环蛋白系统也受GnT-III调节。β-连环蛋白的磷酸化被GnT-III抑制，e-钙粘蛋白的表达由GnT-IIIFut控制，8参与N-聚糖上的核心岩藻糖基化。为了解Fut 8基因的生理学意义，我们建立了Fut 8基因缺陷小鼠模型。这种小鼠表现出严重的生长迟缓，70%的小鼠在出生后3天内死亡。有趣的是，病理学分析显示小鼠肺气肿样病变。这种变化的机制是由于TGF β受体调节异常，导致MMP表达增加。

项目成果

Plasma 3-deoxyglucosone elevation in chronic renal failure is associated with increased aldose reductase in erythrocytes

• DOI: 10.1053/ajkd.2002.34884
• 发表时间: 2002-09-01
• 期刊: AMERICAN JOURNAL OF KIDNEY DISEASES
• 影响因子: 13.2
• 作者: Hasuike, Y;Nakanishi, T;Takamitsu, Y
• 通讯作者: Takamitsu, Y

A specific detection of GIcNAc{beta}1-6Man{alpha}1 branches in N-linked glycoproteins based on the specificity of N-acetylglucosaminyltransferase VI.

基于 N-乙酰氨基葡萄糖转移酶 VI 的特异性，对 N-连接糖蛋白中的 GlcNAc{beta}1-6Man{α}1 分支进行特异性检测。

• 发表时间: 2006
• 期刊: Glycobiology (In press)
• 作者: M.Matsugi;K.Murata;K.Gotanda;H.Nambu;G.Anilkumar;K.Matsumoto;Y.Kita;Tae Watanabe
• 通讯作者: Tae Watanabe

A remodeling system of the 3'-sulfo-Lewis a and 3'-sulfo-Lewis x epitopes.

3-磺基-Lewis a 和 3-磺基-Lewis x 表位的重塑系统。

• 发表时间: 2001
• 期刊: J Biol Chem 276
• 作者: Tsushima F;Iwai H;Otsuki N;Abe M;Hirose S;Yamazaki T;Akiba H;Yagita H;Takahashi Y;Omura K;Okumura K;Azuma M.;Ikeda N et al.
• 通讯作者: Ikeda N et al.

Down-regulation of the alpha-Gal epitope expression in N-glycans of swine endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene. Modulation of the biosynthesis of terminal structures by a bisecting GlcNAc.

通过转染 N-乙酰氨基葡萄糖转移酶 III 基因，下调猪内皮细胞 N-聚糖中 α-Gal 表位的表达。

• 发表时间: 2001
• 期刊: J Biol Chem 276
• 作者: Koyota;S.;Ikeda;Y.;Miyagawa;S.;Ihara;H.;Koma;M.;Honke;K.;Shirakura;R.;Taniguchi;N.
• 通讯作者: N.

Transgenic pigs with human N-acetylglucosaminyltransferase III.

具有人 N-乙酰氨基葡萄糖转移酶 III 的转基因猪。

• 发表时间: 2001
• 期刊: Transplant Proc 33
• 作者: Miyagawa;S.;Murakami;H.;Murase;A.;Nakai;R.;Koma;M.;Koyota;S.;Matsunami;K.;Takahagi;Y.;Fujimura;T.;Shigehisa;T.;Nagashima;H.;Shirakura;R.;Taniguchi;N.
• 通讯作者: N.