脱酰胺使RelA从介导炎症转变为有氧糖酵解
400-123-4567
网站公告: 欢迎光临我们公司的网站...
联系方式contact us
地址:广东省广州市天河区88号
电话:400-123-4567
传真:+86-123-4567
搜狐新闻 当前位置:主页 > 搜狐新闻 >

脱酰胺使RelA从介导炎症转变为有氧糖酵解

文章来源:美高梅官方    时间:2020-04-23

本期文章:《细胞—代谢》:Online/在线发表

美国南加州大学Pinghui Feng研究组取得新进展,他们的最新工作发现,脱酰胺使RelA从介导炎症转变为有氧糖酵解。该研究于2020年4月22日在线发表于《细胞—代谢》。

研究人员发现,氨基甲酰磷酸合成酶、天冬氨酰转氨甲酰水解酶和二氢乳清酶(CAD)使癌细胞中NF-κB的RelA亚基脱酰胺,从而促进有氧糖酵解并为肿瘤发生中的增殖供能。

 

这种翻译后修饰可将RelA功能从介导NF-κB响应基因的表达转换为糖酵解酶的表达,从而分流细胞对有氧糖酵解的炎症反应。

 

此外,研究人员分析了多种人类癌细胞系,发现高CAD表达和RELA突变的一部分与RelA脱酰胺作用有关。并通过使用关键糖酵解酶的抑制剂,他们验证了RelA脱酰胺作用在癌细胞系肿瘤发生中的关键作用。这项工作表明,蛋白质脱酰胺作用选择性地指定基因表达和随后的生物学过程。

 

据了解,细胞增殖和炎症是两个在代谢上需要的生物过程。这些竞争过程如何在同一单元中有选择地执行仍然是未知的。

 

附:英文原文

Title: Deamidation Shunts RelA from Mediating Inflammation to Aerobic Glycolysis

Author: Jun Zhao, Mao Tian, Shu Zhang, Alireza Delfarah, Ruoyun Gao, Youliang Rao, Ali Can Savas, Anjie Lu, Larissa Bubb, Xiao Lei, Rosa Moshirian, Wenjie Zhu, Cheng Peng, Taijiao Jiang, Lin Chen, Nicholas A. Graham, Pinghui Feng

Issue&Volume: 2020-04-22

Abstract: Cell proliferation and inflammation are two metabolically demanding biological processes.How these competing processes are selectively executed in the same cell remains unknown.Here, we report that the enzyme carbamoyl-phosphate synthetase, aspartyl transcarbamoylase,and dihydroorotase (CAD) deamidates the RelA subunit of NF-κB in cancer cells to promoteaerobic glycolysis and fuel cell proliferation in tumorigenesis. This post-translationalmodification switches RelA function from mediating the expression of NF-κB-responsivegenes to that of glycolytic enzymes, thus shunting the cell’s inflammatory responseto aerobic glycolysis. Further, we profiled diverse human cancer cell lines and foundthat high CAD expression and a subset of RELA mutations correlated with RelA deamidation. And by use of inhibitors of key glycolyticenzymes, we validated the pivotal role of RelA deamidation in tumorigenesis of cancercell lines. This work illuminates a mechanism by which protein deamidation selectivelyspecifies gene expression and consequent biological processes.

DOI: 10.1016/j.cmet.2020.04.006

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30188-1

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx

【返回列表页】
地址:广东省广州市天河区88号    座机:400-123-4567    手机:138-0000-8899
版权所有:Copyright © 2002-2019 美高梅开户注册 版权所有    技术支持:织梦58    ICP备案编号:ICP备********号