CYTOTOXICITY OF A RIBONUCLEASE/ANGIOGENIN HYBRID

血管生成素(Angigenin，Ang)是核糖核酸酶家族的一员，具有诱导血液生成的作用 血管形成(血管生成)。ANG有限但必要的， 核糖核酸酶活性。最近，一种血管紧张素/核糖核酸酶A杂合蛋白 (RNANG)，显示血管生成活性，是通过取代 RNaseA中的外部循环和Ang中的相应循环。目的 这项提案中提出的研究内容之一是研究分子基础。 用于细胞识别和结合、核定位以及 Ang和RNANG的细胞毒性。定点突变将被用于 产生具有不同活性和特异性的Ang/RNaseA杂合蛋白。 突变体在体内促进/抑制血管生成的能力将是 评估过了。对细胞生长速度和细胞毒性的影响 针对一组内皮细胞和肿瘤细胞进行筛选，这些细胞由他们的 内化RNANG的能力。对血管生成的基本认识 理想情况下，活动将导致开发一种治疗血液控制的方法。 肿瘤生长和转移中的血管形成。

Angiogenin (ANG), a member of the RNase family of proteins, induces blood vessel formation (angiogenesis). ANG has limited, but necessary, ribonuclease activity. Recently, an ANG/ribonuclease A hybrid protein (RNANG), displaying angiogenic activity, was created by replacing an exterior loop in RNase A with the corresponding loop from ANG. The purpose of the research presented in this proposal is to study the molecular basis for cellular recognition and binding, nuclear localization, and the cytotoxicity of ANG and RNANG. Site-directed mutagenesis will be used to create ANG/RNase A hybrid proteins of varying activity and specificity. The ability of the mutants to promote/inhibit angiogenesis in vivo will be assessed. Effects on cellular growth rate and cytotoxicity will be screened against a panel of endothelial and tumor cells selected by their ability to internalize RNANG. A fundamental understanding of angiogenic activity would ideally lead to developing a therapeutic control of blood vessel formation in tumor growth and metastasis.