N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma.
N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma.
复制标题
CD147 上 Asn152 的 N 联糖基化影响蛋白质折叠和稳定性：促进肝细胞癌的肿瘤转移
DOI：
10.1038/srep35210
复制
发表时间：
2016-11-21
影响因子：
4.6
通讯作者：
Jiang JL
中科院分区：
文献类型：
--
作者：
Li JH;Huang W;Lin P;Wu B;Fu ZG;Shen HM;Jing L;Liu ZY;Zhou Y;Meng Y;Xu BQ;Chen ZN;Jiang JL
分化簇147（CD 147），也称为细胞外基质金属蛋白酶诱导剂，是一种跨膜糖蛋白，部分通过N-糖基化修饰介导致癌过程。N-糖基化已被证明有助于恶性转化过程中CD 147功能的调节。然而，CD 147的位点特异性糖基化在其在肝细胞癌细胞中的功能缺陷中所起的作用需要确定。在这里，我们证明了在CD 147上Asn 152的N-糖基化的修饰强烈促进肝细胞癌（HCC）的侵袭和迁移。去除Asn 152处的N-聚糖后，CD 147更容易被ER定位的泛素连接酶介导的内质网相关降解（ERAD）降解。此外，Asn 152处的N-连接聚糖是CD 147在ER中获得和维持正确折叠所必需的。此外，Asn 152处的N-连接聚糖作为识别基序发挥作用，其直接由CNX质量控制系统介导。基于滞留的ER分子伴侣系统中的两个阶段驱动ER定位的CD 147运输降解。CD 147上Asn 152处N-连接糖基化的缺失显著抑制原位肿瘤转移。这些数据可能有助于阐明通过糖基化对CD 147的分子调控，并为开发靶向CD 147上Asn 152的N-聚糖的药物提供了有价值的手段。
Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147.
登录
查看更多内容
影响因子：
2.9
作者：
Petrescu, SM;Branza-Nichita, N;Dwek, RA
通讯作者：
Dwek, RA
影响因子：
6.4
作者：
Li, Yu;Xu, Jing;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan
影响因子：
4.8
作者：
KASTURI, L;ESHLEMAN, JR;SHAKINESHLEMAN, SH
通讯作者：
SHAKINESHLEMAN, SH
影响因子：
11.2
作者：
Kong, Ling-Min;Liao, Cheng-Gong;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan
CD133中Asn548的N联糖基化突变降低了其促进肝癌细胞生长的能力
影响因子：
--
作者：
Liu Y;Ren S;Xie L;Cui C;Xing Y;Liu C;Cao B;Yang F;Li Y;Chen X;Wei Y;Lu H;Jiang J
通讯作者：
Jiang J