Molecular mechanism for the development of gastric lesions by Helicobacter pylori infection

幽门螺杆菌（H.携带cagA基因的pylori）菌株比cagA阴性菌株毒力更强，并且与胃腺癌的发展相关。cagA基因产物CagA易位到胃上皮细胞中并定位于质膜的内表面，在那里它在EPIYA基序处经历酪氨酸磷酸化。酪氨酸磷酸化的CagA特异性结合并激活SHP-2酪氨酸磷酸酶和C-末端Src激酶（Csk），从而诱导被称为蜂鸟表型的细长细胞形状。与西方国家分离的幽门螺杆菌相比，东亚国家分离的幽门螺杆菌CagA菌株表现出更强的SHP-2结合活性和更大的病理生物学活性。因此，感染东亚cagA阳性幽门螺杆菌的人群可能比感染西方cagA阳性或cagA阴性菌株的人群患胃癌的风险更大。 ...更多信息 n人类肿瘤中的基因变化。在携带K-ras突变的肿瘤中，致癌K-Ras的存在不仅是肿瘤发生所必需的，而且是维持转化表型所必需的。ESXR 1是一种含有人类配对样同源结构域的蛋白。全长ESXR 1蛋白被蛋白水解加工成含有同源结构域的N-末端片段和C-末端片段。全长ESXR 1和C-末端片段定位于细胞质，而N-末端含有同源结构域的ESXR 1片段仅定位于细胞核内。N-末端ESXR 1片段通过与人K-ras基因第一内含子内存在的TAATGTTATTA序列结合来抑制K-ras mRNA转录。在携带突变的K-ras的人癌细胞中表达N-末端ESXR 1片段降低K-Ras水平并抑制肿瘤细胞增殖。ESXR 1作为K-ras基因转录抑制因子的鉴定对于靶向致癌K-ras的癌症治疗的发展具有重要意义。少

Helicobacter pylori (H. pylori) strains carrying the cagA gene are more virulent than cagA-negative strains and are associated with the development of gastric adenocarcinoma. The cagA gene product, CagA, is translocated into gastric epithelial cells and localizes to the inner surface of the plasma membrane, where it undergoes tyrosine phosphorylation at the EPIYA motifs. Tyrosine-phosphorylated CagA specifically binds and activates SHP-2 tyrosine phosphatase and the C-terminal Src kinase (Csk), thereby inducing an elongated cell shape termed the hummingbird phenotype. CagA species of H.pylori isolated in East Asian countries exhibit stronger SHP-2 binding activity and greater pathobiological activity than those isolated in Western countries. Thus, populations infected with East Asian cagA-positive H.pylori may be at greater risk for gastric cancer than those infected with Western cagA-positive or cagA-negative strains.Gain-of-function mutation of the K-ras gene is one of the most commo … More n genetic changes in human tumors. In tumors carrying K-ras mutation, the presence of oncogenic K-Ras is not only essential for the tumorigenesis but also necessary for maintenance of the transformed phenotype. ESXR1 is a human paired-like homeodomain-containing protein. The full-length ESXR1 protein is proteolytically processed into an N-terminal fragment containing the homeodomain and a C-terminal fragment. The full-length ESXR1 and the C-terminal fragment are localized to the cytoplasm, whereas the N-terminal homeodomain-containing ESXR1 fragment is exclusively localized within the nucleus. The N-terminal ESXR1 fragment represses K-ras mRNA transcription by binding to the TAATGTTATTA sequence present within the first intron of the human K-ras gene. Expression of the N-terminal ESXR1 fragment in human carcinoma cells that carry mutated K-ras reduces the level of K-Ras and inhibits the tumor cell proliferation. Identification of ESXR1 as a transcriptional repressor of the K-ras gene has an important implication for the development of cancer therapy that targets oncogenic K-ras. Less