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。
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.
作者
虢婷
尚梦宇
郭茵
黄卫人
GUO Ting;SHANG Mengyu;GUO Yin;HUANG Weiren(Graduate School,Guangxi University of Chinese Medicine,Nanning 530200,China;School of Basic Medical Sciences,Health Science Center,Shenzhen University,Shenzhen 518061,China;Department of Pharmacology,School of Medicine,Shantou University,Shantou 515041,China;Instibute of Translational Medicine,The Second People’s Hospital of Shenzhen,Shenzhen 518025,China)
出处
《肿瘤防治研究》
CAS
2024年第6期475-483,共9页
Cancer Research on Prevention and Treatment
基金
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)。
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
ERK1/2
Tumor
Targeted therapy
Post-translational modifications
Dimerization
Small molecule inhibitor
