Protein neddylation and its alterations in human cancers for targeted therapy.
Protein neddylation and its alterations in human cancers for targeted therapy.
复制标题
蛋白质 neddylation 及其在人类癌症中的改变用于靶向治疗。
DOI：
10.1016/j.cellsig.2018.01.009
复制
发表时间：
2018-04
影响因子：
4.8
通讯作者：
Jia L
中科院分区：
文献类型：
--
作者：
Zhou L;Zhang W;Sun Y;Jia L
泛素化修饰是一种将泛素样蛋白NEDD8与底物蛋白结合的翻译后修饰，是调节蛋白质功能的重要生化过程。最有特征的类化修饰底物是cullin - ring连接酶（CRLs）的cullin亚基，它是E3泛素连接酶中最大的家族，通过促进泛素化和随后多种关键调节蛋白的降解来控制许多重要的生物过程，包括肿瘤发生。最近，越来越多的实验证据有力地表明，蛋白类化修饰过程在多种人类癌症中升高，为其作为一种有吸引力的抗癌治疗策略提供了合理的理由。事实上，目前处于I/II期临床试验的一种E1 nedd8激活酶的小分子抑制剂MLN4924（也称为pevonedistat）通过诱导细胞周期阻滞、凋亡、衰老和自噬，以细胞类型和环境依赖的方式发挥显著的抗癌作用。在这里，我们总结了该领域的最新进展，主要集中在验证类化修饰作为一个有前途的抗癌靶点的临床前研究。
Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins. Recently, increasing pieces of experimental evidence strongly indicate that the process of protein neddylation modification is elevated in multiple human cancers, providing sound rationale for its targeting as an attractive anticancer therapeutic strategy. Indeed, neddylation inactivation by MLN4924 (also known as pevonedistat), a small molecule inhibitor of E1 NEDD8-activating enzyme currently in phase I/II clinical trials, exerts significant anticancer effects by inducing cell cycle arrest, apoptosis, senescence and autophagy in a cell-type and context dependent manner. Here, we summarize the latest progresses in the field with a major focus on preclinical studies in validation of neddylation modification as a promising anticancer target.
登录
查看更多内容
自噬和neddylation途径的协同抑制作为靶向肝癌的新型治疗方法
影响因子：
--
作者：
Chen P;Hu T;Liang Y;Jiang Y;Pan Y;Li C;Zhang P;Wei D;Li P;Jeong LS;Chu Y;Qi H;Yang M;Hoffman RM;Dong Z;Jia L
通讯作者：
Jia L
影响因子：
13.3
作者：
Carew, Jennifer S.;Nawrocki, Steffan T.;Cleveland, John L.
通讯作者：
Cleveland, John L.
影响因子：
16
作者：
Brownell, James E.;Sintchak, Michael D.;Dick, Lawrence R.
通讯作者：
Dick, Lawrence R.
Neddylation 抑制通过 ATF4-CHOP-DR5 轴激活人食管癌细胞的外源性凋亡途径
影响因子：
11.5
作者：
Chen, Ping;Hu, Tao;Jia, Lijun
通讯作者：
Jia, Lijun
影响因子：
14.5
作者：
Bloom, J;Pagano, M
通讯作者：
Pagano, M