基质O-糖基化活跃调节细胞外蛋白质溶解
Elizabeta Madzharova1, Fabio Sabino1, Konstantinos Kalogeropoulos1
1Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Protein science : a publication of the Protein Society
|July 29, 2024
概括
截断的O-糖化,特别是Tn抗原,增强了矩阵金属蛋白酶9 (MMP9) 的活性,并改变了乳腺癌细胞中的蛋白质加工. 这表明O-甘氨酸与蛋白质溶解之间存在联系,影响癌症的进展.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 细胞外蛋白解调节细胞功能,并与疾病有关.
- 翻译后修饰 (PTMs),包括O-糖化和蛋白质分解,相互作用控制细胞平衡.
- 矩阵金属蛋白酶 (MMPs) 和N-乙银胺 (GalNAc) 型O-糖化是关键的细胞外PTMs.
研究的目的:
- 调查截断的O-甘氨酸 (Tn抗原) 如何影响蛋白质分解处理,特别是MMP9活性.
- 探索O-甘氨酸切割对细胞外蛋白质组和细胞外域脱落的影响.
- 了解癌症中O-GalNAc糖化和蛋白解之间的相互作用.
主要方法:
- 使用MDA-MB-231乳腺癌细胞与非活化的C1GALT1特异性伴侣1 (COSMC) 诱导Tn抗原.
- 用于对基质的终端氨基同位素标记 (TAILS) 进行定量蛋白质组和N-终端组分析.
- 评估了MMP9特异性的蛋白质分解过程,并确定了新的ectodomain shedding事件.
主要成果:
- 截断的O-甘氨酸 (Tn抗原) 导致细胞外蛋白质组中增强的MMP9-介导蛋白解.
- 在切断O-糖的细胞中观察到整体蛋白质组的显著变化.
- 发现了由O-甘氨酸切断调节的新型生殖区脱落实例.
结论:
- 成熟的O-糖化对调节蛋白质分解加工和维持蛋白质组稳定至关重要.
- 截断的O-甘氨酸可以增加蛋白质对蛋白质分解的敏感性,特别是通过MMP9.
- 蛋白质分解和O-GalNAc糖化之间的相互作用可能会影响癌症表型.
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