Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling.
Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling.
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DOI：
10.3390/ijms19020580
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发表时间：
2018-02-15
影响因子：
5.6
通讯作者：
Dall'Olio F
中科院分区：
文献类型：
--
作者：
Ferreira IG;Pucci M;Venturi G;Malagolini N;Chiricolo M;Dall'Olio F
糖基化是一种非常常见且功能重要的翻译后蛋白质修饰，其在癌症中经历深刻的变化。生长和死亡因子受体和质膜糖蛋白在被细胞外配体激活后触发信号转导级联，是几种分子抗癌药物的靶点。在这篇综述中，我们提供了一个完整的图片的机制，其中糖基化影响的活性生长和死亡因子受体在正常和病理条件。糖基化通过三种非相互排斥的基本机制影响受体活性：（1）通过直接调节受体的细胞内转运、配体结合、寡聚化和信号传导;（2）通过受体碳水化合物结构与半乳糖凝集素的结合，形成调节质膜上受体周转的晶格;（3）通过受体与膜微域内神经节苷脂的相互作用。一些碳水化合物链，例如核心岩藻糖和β 1，6-分支，对所有受体发挥刺激作用，而其他结构对不同受体或在不同细胞环境中发挥相反的作用。鉴于糖基化在调节受体活性中所起的关键作用，靶向生长因子受体糖表位的下一代药物的开发应被视为治疗上令人感兴趣的目标。
Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1) by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2) through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3) by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.
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影响因子：
3.7
作者：
D'Haene N;Sauvage S;Maris C;Adanja I;Le Mercier M;Decaestecker C;Baum L;Salmon I
通讯作者：
Salmon I
DOI：
10.1158/1078-0432.ccr-09-3331
发表时间：
2010-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Contessa JN;Bhojani MS;Freeze HH;Ross BD;Rehemtulla A;Lawrence TS
通讯作者：
Lawrence TS
影响因子：
4.8
作者：
Guo, Hua-Bei;Randolph, Matthew;Pierce, Michael
通讯作者：
Pierce, Michael
影响因子：
4.4
作者：
Guan, Feng;Handa, Kazuko;Hakomori, Sen-itiroh
通讯作者：
Hakomori, Sen-itiroh
影响因子：
3.7
作者：
Chu C;Bottaro DP;Betenbaugh MJ;Shiloach J
通讯作者：
Shiloach J