基于ERK1/2翻译后修饰调控及空间性调节的抗癌策略研究进展
Research Progress of Anti-cancer Strategies Based on ERK1/2 Post-translational Modification and Spatial Regulation
虢婷 1尚梦宇 2郭茵 3黄卫人4
作者信息
- 1. 530200 南宁,广西中医药大学研究生院
- 2. 518061 深圳,深圳大学医学部基础医学院
- 3. 515041 汕头,汕头大学医学院药理学教研室
- 4. 530200 南宁,广西中医药大学研究生院;518025 深圳,深圳市第二人民医院转化医学研究院
- 折叠
摘要
ERK1/2是一种介导细胞信号转导的关键蛋白,参与调节细胞的染色质重塑、核解体、增殖、存活、代谢、迁移和分化等生物学过程.其过度激活与癌症的发生进展密切相关,机制表现为上游通路分子或调节因子的基因突变使ERK1/2过度激活及针对上述靶点进行抑制后的ERK1/2再激活.因而ERK1/2为一个有潜在价值的靶点.本文对ERK1/2的翻译后修饰调控及空间性调节的机制研究和相应小分子抑制剂的应用现状进行了讨论,总结并展望了目前靶向调控ERK1/2的抗癌策略及针对潜在靶点展开探索的可能性,为ERK1/2作为抗癌理想靶点的开发性研究提供了新思路.
Abstract
ERK1/2 is a key protein that mediates cell signal transduction,and it is involved in regulating biological processes such as chromatin remodeling,nuclear disintegration,proliferation,survival,metabolism,and cell migration and differentiation.Its overactivation is closely related to the occurrence and progression of cancer,and the mechanism is manifested as the overactivation of ERK1/2 by gene mutations of upstream pathway molecules or regulators and the reactivation of ERK1/2 after inhibition against the above targets.ERK1/2 is a potentially valuable target.In this review,the mechanism of post-translational modification and spatial regulation of ERK1/2 and the application status of corresponding small-molecule inhibitors were discussed.The current antitumor strategy of targeting and regulating ERK1/2 was summarized,and the possibility of exploring potential targets was elucidated,thus providing new insights into the developmental research of ERK1/2 as an ideal anticancer target.
关键词
ERK1/2/肿瘤/靶向治疗/翻译后修饰/二聚化/小分子抑制剂Key words
ERK1/2/Tumor/Targeted therapy/Post-translational modifications/Dimerization/Small mole-cule inhibitor引用本文复制引用
基金项目
国家重点研发计划(2019YFA0906000)
国家自然科学基金青年科学基金(82203459)
深圳市科技创新项目(JCYJ20200109120016553)
出版年
2024
国家科技期刊平台
NSTL
万方数据