E3泛素连接酶在肿瘤发生发展中的作用机制研究进展OA

E3 ubiquitin ligases,as core components of the ubiquitin-proteasome system,play crucial roles in maintaining intracellular protein homeostasis by mediating the ubiquitination of target proteins.In recent years,the abnormal regulatory mechanisms of E3 ubiquitin ligases in tumor initiation and progression have emerged as a research hotspot.However,the specific functions and regulatory mechanisms of E3 ubiquitin ligases with different structural types in tumors still need to be systematically elucidated.Therefore,under-standing the mechanisms of different types of E3 ubiquitin ligases in tumorigenesis has important theoretical and clinical significance for clarifying the molecular pathological mechanisms of cancers and developing novel targeted therapeutic strategies.This review first describes the classification and structural characteristics of E3 ubiquitin ligases,focusing on the domain composition and ubiquitin transfer mechanisms of the homolo-gous to E6AP carboxyl-terminus(HECT),really interesting new gene(RING),RING-between-RING(RBR),and U-box families.Next,the dual functions,targeted proteins,and related signaling pathways of several typical E3 ubiquitin ligases in four common high-incidence malignant tumors(lung cancer,liver cancer,co-lorectal cancer,and breast cancer)are extensively discussed,and the molecular mechanisms by which E3 ubi-quitin ligases regulate tumor progression and drug resistance are elucidated.Finally,the latest research progress and potential therapeutic strategies targeting E3 ubiquitin ligases in cancer treatment are summa-rized,and the challenges including the efficacy and safety risks of such strategies are discussed.Future ef-forts should further integrate multidisciplinary approaches,such as structural biology,high-throughput screen-ing,and artificial intelligence-assisted drug design,to promote the application of E3 ubiquitin ligases in cancer diagnosis and treatment,offering new prospects for improving the prognosis and therapeutic outcomes of cancer patients.