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测量黏蛋白结构域糖蛋白在癌症中的多方面作用。

Measuring the multifaceted roles of mucin-domain glycoproteins in cancer.

机构信息

Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, United States.

Department of Urology, Stanford University School of Medicine, Stanford, CA, United States.

出版信息

Adv Cancer Res. 2023;157:83-121. doi: 10.1016/bs.acr.2022.09.001. Epub 2022 Oct 8.

DOI:10.1016/bs.acr.2022.09.001
PMID:36725114
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10582998/
Abstract

Mucin-domain glycoproteins are highly O-glycosylated cell surface and secreted proteins that serve as both biochemical and biophysical modulators. Aberrant expression and glycosylation of mucins are known hallmarks in numerous malignancies, yet mucin-domain glycoproteins remain enigmatic in the broad landscape of cancer glycobiology. Here we review the multifaceted roles of mucins in cancer through the lens of the analytical and biochemical methods used to study them. We also describe a collection of emerging tools that are specifically equipped to characterize mucin-domain glycoproteins in complex biological backgrounds. These approaches are poised to further elucidate how mucin biology can be understood and subsequently targeted for the next generation of cancer therapeutics.

摘要

黏蛋白型糖蛋白是高度 O-糖基化的细胞表面和分泌蛋白,可作为生化和生物物理调节剂。黏蛋白的异常表达和糖基化是许多恶性肿瘤的显著特征,但在癌症糖生物学的广阔领域中,黏蛋白型糖蛋白仍然是一个谜。本文通过研究黏蛋白的分析和生化方法,从多个角度综述了黏蛋白在癌症中的作用。我们还描述了一系列新兴工具,这些工具专门用于在复杂的生物学背景下对黏蛋白结构域糖蛋白进行特征分析。这些方法有望进一步阐明如何理解黏蛋白生物学,并为下一代癌症治疗方法提供靶标。

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本文引用的文献

1
Design of a mucin-selective protease for targeted degradation of cancer-associated mucins.设计一种粘蛋白选择性蛋白酶,用于靶向降解与癌症相关的粘蛋白。
Nat Biotechnol. 2024 Apr;42(4):597-607. doi: 10.1038/s41587-023-01840-6. Epub 2023 Aug 3.
2
A mechanism of gene evolution generating mucin function.一种产生粘蛋白功能的基因进化机制。
Sci Adv. 2022 Aug 26;8(34):eabm8757. doi: 10.1126/sciadv.abm8757.
3
Structural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut.
Biosensors (Basel). 2024 Jul 4;14(7):330. doi: 10.3390/bios14070330.
4
Bringing enzymes to the proximity party.让酶参与到邻近反应中。
RSC Chem Biol. 2023 Sep 29;4(12):986-1002. doi: 10.1039/d3cb00084b. eCollection 2023 Nov 29.
5
Aberrant Glycosylation as Immune Therapeutic Targets for Solid Tumors.异常糖基化作为实体瘤的免疫治疗靶点
Cancers (Basel). 2023 Jul 8;15(14):3536. doi: 10.3390/cancers15143536.
揭示人类肠道粘蛋白酶切割聚集 O-糖链补丁糖蛋白的结构和机制研究
Nat Commun. 2022 Jul 26;13(1):4324. doi: 10.1038/s41467-022-32021-9.
4
Current strategies for characterization of mucin-domain glycoproteins.目前用于糖蛋白中粘蛋白结构域特征分析的策略。
Curr Opin Chem Biol. 2022 Aug;69:102174. doi: 10.1016/j.cbpa.2022.102174. Epub 2022 Jun 22.
5
Revealing the human mucinome.揭示人类黏蛋白组。
Nat Commun. 2022 Jun 20;13(1):3542. doi: 10.1038/s41467-022-31062-4.
6
Sialylated glycoproteins as biomarkers and drivers of progression in prostate cancer.唾液酸化糖蛋白作为前列腺癌的生物标志物和进展驱动因子。
Carbohydr Res. 2022 Sep;519:108598. doi: 10.1016/j.carres.2022.108598. Epub 2022 Jun 1.
7
Reading the glyco-code: New approaches to studying protein-carbohydrate interactions.解读糖码:研究蛋白质-碳水化合物相互作用的新方法。
Curr Opin Struct Biol. 2022 Aug;75:102395. doi: 10.1016/j.sbi.2022.102395. Epub 2022 May 30.
8
Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences.结构导向的阿克曼氏菌粘蛋白选择性金属蛋白酶突变改变了底物偏好。
J Biol Chem. 2022 May;298(5):101917. doi: 10.1016/j.jbc.2022.101917. Epub 2022 Apr 9.
9
Analysis of Viral Spike Protein N-Glycosylation Using Ultraviolet Photodissociation Mass Spectrometry.利用紫外光解离质谱分析病毒刺突蛋白 N-糖基化。
Anal Chem. 2022 Apr 19;94(15):5776-5784. doi: 10.1021/acs.analchem.1c04874. Epub 2022 Apr 7.
10
Seeing the forest through the trees: characterizing the glycoproteome.透过现象看本质:糖蛋白质组学的特征。
Trends Biochem Sci. 2022 Jun;47(6):492-505. doi: 10.1016/j.tibs.2022.02.007. Epub 2022 Mar 17.