研究动态
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异常的蛋白质糖基化:对诊断和免疫治疗的影响。

Aberrant protein glycosylation: Implications on diagnosis and Immunotherapy.

发表日期:2023 Apr 06
作者: Rashmi Bangarh, Chainika Khatana, Simranjeet Kaur, Anchita Sharma, Ankur Kaushal, Samarjeet Singh Siwal, Hardeep Singh Tuli, Kuldeep Dhama, Vijay Kumar Thakur, Reena V Saini, Adesh K Saini
来源: BIOTECHNOLOGY ADVANCES

摘要:

糖基化介导的蛋白质后翻译修饰对调节许多基本过程至关重要,如细胞分裂、分化、免疫应答和细胞间相互作用。调控蛋白质的N-或O-糖基化模式的改变,如转录因子或细胞受体,会导致许多疾病,包括癌症。这些变化导致肿瘤细胞的微观和宏观异质性。本文回顾了O-和N-糖基化在自身免疫和癌症中的调控作用和异常糖基化的研究。细胞糖复合物的变化可能来自于糖苷酶或糖基转移酶(如N-乙酰葡糖胺转移酶V、FUT8、ST6Gal-I、DPAGT1等)的表达变化,影响目标蛋白质的糖基化,导致细胞转化。此外,糖基基因的突变会影响免疫细胞上的糖基化模式,导致其他相关表现,如促炎症或抗炎症作用。近年来,对糖复合物与癌症的了解表明,它既可用于诊断/预后,也可用于免疫治疗。涉及到患者样本和癌症模型的蛋白组质谱学、位点和结构特异性的糖蛋白组学,以及转录组/基因组研究揭示了糖基化调控在癌症生物学中的重要性。新兴技术的发展,如凝集素微阵列,已经促进了糖类和糖基化结构与功能的研究。新开发的设备可以实现高通量、高速度和精确的异常糖基化研究。本文还讨论了糖基化的新兴技术和临床应用。版权所有©2023 Elsevier Inc.
Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.Copyright © 2023. Published by Elsevier Inc.