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血管生成素(angiogenin,ANG)能有效促进血管生成和肿瘤细胞增殖,在肿瘤发生发展中起重要作用.其主要分子机制是通过核转位和激活PI3K/AKT/m TOR信号通路,刺激r RNA转录和核糖体生成.ANG也被发现在肌萎缩侧索硬化症(ALS)和帕金森病(PD)患者中存在基因编码区的功能突变,表明其在运动神经元生理方面发挥作用,其缺陷是神经退行性疾病的一个危险因素.核糖核酸酶抑制因子(ribonuclease inhibitor,RI)是胞内酸性蛋白质,由460个氨基酸残基组成,分子质量约为50 k D,当其与核糖核酸酶A(RNase A)结合形成复合物后,可抑制RNase A的90%以上活性,从而有效调节细胞内RNA水平.ANG具有低核糖核酸酶活性,是RNase超家族一员,与RNase A有着高度保守的同源顺序.序列、结构和酶学等分析表明,RI也能够与ANG紧密结合,且得到体外实验的证明.研究发现,RI具抑癌基因功能;RI与ANG在细胞内共定位;Co-IP和GST pull-down证实其相互作用,获取了RI与ANG在体内结合的直接证据;RI与AKT磷酸化表达负相关.在膀胱癌细胞及临床标本中证实了RI与ANG和PI3K/AKT通路分子表达的相关性及与肿瘤细胞生长与转移的关系.在细胞和动物模型研究表明,RI调节ANG活性的功能及其分子机制,即RI通过结合ANG而封锁其核转位和调控PI3K/AKT/m TOR信号通路及其相关通路交互应答(cross-talk)的能力,从而抑制肿瘤生长及转移.RI是一个有希望的抗肿瘤蛋白新药和血管生成抑制剂,可望成为基因治疗的靶基因.
Angiogenin (ANG) can effectively promote angiogenesis and tumor cell proliferation and play an important role in tumorigenesis and development.The main molecular mechanism is angiotensin (ANG) stimulating r RNA through nuclear translocation and activation of PI3K / AKT / m TOR signaling pathway Transcription and ribosomal generation .ANG is also found to have a functional mutation in the coding region of genes in patients with amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD), suggesting that it plays a role in motoneuron physiology with defects Is a risk factor for neurodegenerative diseases.Ribonuclease inhibitor (RI) is an intracellular acidic protein consisting of 460 amino acid residues and has a molecular mass of about 50 kD. When it binds to ribonuclease A (RNase A) to form a complex that inhibits more than 90% of RNase A activity and effectively regulates intracellular RNA levels .ANG has a low ribonuclease activity and is a member of the RNase superfamily, highly conserved with RNase A Sequence, structure and enzymatic analysis showed that RI could also bind tightly with ANG and was proved by in vitro experiments.It is found that RI has anti-oncogene function, co-localization of RI and ANG in cells, co- IP and GST pu ll-down to confirm the interaction between RI and ANG in the body to obtain the direct evidence of RI and AKT phosphorylation expression was negative correlation in bladder cancer cells and clinical specimens confirmed RI and PI3K / AKT pathway molecule expression And their relationship with the growth and metastasis of tumor cells.Studies in cellular and animal models show that RI regulates the function of ANG activity and its molecular mechanism that RI blocks its nuclear translocation and regulates PI3K / AKT / m TOR by binding to ANG Signaling pathways and their related pathways to inhibit tumor growth and metastasis.RI is a promising new anti-tumor protein and angiogenesis inhibitor that is expected to be the target of gene therapy.