Notch信号通路——对健康和疾病的机械论观点  

The Notch Signaling Pathway:Mechanistic Insights in Health and Disease

作　　者：Yao Meng Zhihan Bo Xinyi Feng Xinyi Yang Penny A.Handford 

机构地区：[1]Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [2]Department of Biochemistry,University of Oxford,Oxford OX13QU,UK [3]State Key Laboratory of Respiratory Health and Multimorbidity,Beijing 100050,China

出　　处：《Engineering》2024年第3期212-232,共21页工程（英文）

基　　金：supported by the Medical Research Council (MRC)Grant (MR/V008935/1);supported by the National Natural Science Foundation of China (82304596);the Fundamental Research Funds for the Central Universities (3332022057);the CAMS Innovation Fund for Medical Sciences (2022-I2M-1-016);supported by the National Natural Science Foundation of China (81973383).

摘　　要：The Notch signaling pathway is evolutionarily conserved across metazoan species and plays key roles in many physiological processes.The Notch receptor is activated by two families of canonical ligands(Deltalike and Serrate/Jagged)where both ligands and receptors are single-pass transmembrane proteins usually with large extracellular domains,relative to their intracellular portions.Upon interaction of the core binding regions,presented on opposing cell surfaces,formation of the receptor/ligand complex initiates force-mediated proteolysis,ultimately releasing the transcriptionally-active Notch intracellular domain.This review focuses on structural features of the extracellular receptor/ligand complex,the role of posttranslational modifications in tuning this complex,the contribution of the cell membrane to ligand function,and insights from acquired and genetic diseases.

关 键 词：Notch signaling pathway Structural biology GLYCOSYLATION Genetic disorders CANCER Pharmacological agents 

分 类 号：Q75[生物学—分子生物学]