NOTCH2编码蛋白是一种跨膜受体，可以作为致癌基因和抑癌基因发挥作用。NOTCH2作为跨膜受体，参与进化上保守的细胞-细胞信号转导途径。NOTCH2受体与相邻细胞上的配体分子的相互作用导致γ-分泌酶对NOTCH2的蛋白水解。然后，裂解的细胞内NOTCH1结构域可以激活细胞核中的基因表达并调节细胞分化，生长，增殖，存活和代谢的各个方面。NOTCH2在信号传导中的特定作用根据细胞环境而变化。NOTCH家族成员经常在各种癌症中发生突变，这些突变可能是功能获得或功能丧失突变。NOTCH2中的截短突变与Hajdu-Cheney综合征相关，在弥漫性大B细胞淋巴瘤（DLBCL）和三阴性乳腺癌中观察到NOTCH2截短突变和局灶性扩增，导致细胞内NOTCH2的稳定和活化。NOTCH2失活突变在实体瘤中最常见，即鳞状细胞癌。

NOTCH2 is a transmembrane receptor that participates in an evolutionarily conserved cell-to-cell signal transduction pathway. Interaction of the NOTCH2 receptor with ligand molecules on adjacent cells results in the proteolytic cleavage of NOTCH2 by the protease termed gamma-secretase. The cleaved intracellular NOTCH2 domain can then activate gene expression in the nucleus and regulate various aspects of cell differentiation, growth, proliferation, survival and metabolism. The specific effects of NOTCH2 signaling vary depending on the cellular context. Truncating mutations in NOTCH2, known to cause Hajdu-Cheney syndrome, interrupt the regulation of the protein degradation process, leading to activation of the NOTCH2 intracellular domain. NOTCH family members are frequently mutated in a variety of cancers, and these mutations can be either gain- or loss-of-function mutations. Truncating mutations and focal amplifications of NOTCH2 have been observed in diffuse large B-cell lymphoma (DLBCL) and triple negative breast cancer, leading to stabilization and activation of intracellular NOTCH2. NOTCH2 inactivating mutations are most common in solid tumors, namely squamous cell carcinomas, and occur as missense, frameshift or nonsense mutations in important NOTCH2 functional domains.

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