Complex N-glycan promotes CD133 mono-ubiquitination and secretion
Complex N-glycan promotes CD133 mono-ubiquitination and secretion
复制标题
复合 N-聚糖促进 CD133 单泛素化和分泌
DOI：
10.1002/1873-3468.13358
复制
发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Wei Yuanyan
中科院分区：
文献类型：
--
作者：
Li Yinan;Shi Danfang;Yang Fan;Chen Xiaoning;Xing Yang;Liang Ziwei;Zhuang Jianhui;Liu Weitao;Gong Ye;Jiang Jianhai;Wei Yuanyan
CD 133是一种广泛使用的肿瘤干细胞的细胞表面标志物，在肿瘤的发生和转移中起重要作用。越来越多的证据表明，CD 133被分泌到细胞外空间。然而，CD 133分泌的潜在机制在很大程度上仍然未知。在这项研究中，我们报告了分泌的CD 133具有复杂型N-糖基化，并被β 1，6 GlcNAc N-聚糖修饰。我们发现苦马豆素抑制CD 133复合物型N-糖基化并不影响CD 133的膜定位，但显著降低了CD 133的分泌并促进其在早期内体中的积累。此外，苦马豆素通过减少其单泛素化和抑制CD 133与Tsg 101之间的相互作用来减少CD 133的分泌。这些发现揭示了CD 133糖基化依赖性分泌的新机制。
CD133 is a widely used cell surface marker of cancer stem cells that plays an important role in tumor initiation and metastasis. Increasing evidence shows that CD133 is secreted to the extracellular space. However, the underlying mechanisms of CD133 secretion remain largely unknown. In this study, we report that secreted CD133 has a complex‐type N‐glycosylation and is modified by beta1,6GlcNAc N‐glycan. We found that inhibition of CD133 complex‐type N‐glycosylation by swainsonine does not affect the membrane localization of CD133, but significantly reduces CD133 secretion and promotes its accumulation in early endosomes. Moreover, swainsonine reduces CD133 secretion by reducing its mono‐ubiquitination and inhibiting the interaction between CD133 and Tsg101. These findings reveal a new mechanism of glycosylation‐dependent secretion of CD133.