SBIR PHASE II: SITE-SPECIFIC ANTIBODIES FOR GLCNACYLATED PROTEINS IN CANCER

o - glcn酰化在细胞周期调节、细胞凋亡和信号转导中起着至关重要的作用。o - glcnnac转移酶对蛋白质的o - glcn酰化修饰通过O-GlcNAcase的活性是可逆的。在丝氨酸或苏氨酸上添加或去除O-GlcNAc片段直接或通过降低磷酸化来调节蛋白质的功能。c-myc蛋白的o - glcn酰化诱导泛素依赖性c-myc降解。p53的glcn酰化可防止p53降解并稳定p53蛋白，在DNA损伤的情况下，通过抑制细胞生长和诱导细胞凋亡对癌细胞有益。为了阐明o - glcn酰化蛋白的功能，有必要开发针对o - glcn酰化蛋白的位点特异性抗体。迄今为止，很少有位点特异性抗体被成功生产出来。缺乏位点特异性的o - glcn酰化抗体阻碍了对位点的检测和定量，从而无法阐明o - glcn酰化分子在生理和疾病中的功能。o - glcnac酰化位点特异性抗体的获得，将促进肿瘤中o - glcnac酰化和磷酸化依赖信号转导通路的机制研究，从而开发o - glcnac酰化诱导的抗癌药物。

O-GlcNAcylation of proteins plays a critical role in cell cycle regulation, apoptosis and signal transduction. Modification of O-GlcNAcylation of proteins by O-GlcNAc transferase is reversible by the activity of O-GlcNAcase. Addition and removal of O-GlcNAc moiety to serine or threonine regulate the function of proteins directly or via decreased phosphorylation. O-GlcNAcylation of c-myc proteins induces ubiquitin-dependent c-myc degradation. GlcNAcylation of p53 prevents p53 degradation and stabilizes p53 proteins, which are beneficial in cancer cells by arresting cell growth and inducing apoptosis in response to DNA damage. To elucidate functions of O-GlcNAcylation of the proteins it is necessary to develop site-specific antibodies for O-GlcNAcylated proteins. Few site-specific antibodies have been successfully produced so far. A lack of site-specific O-GlcNAcylated Abs prevents facile detection and quantitation of the site to elucidate the function of O-GlcNAcylated molecules in physiology and disease. Availability of O-GlcNAcylation site-specific antibodies will facilitate mechanistic studies on O-GlcNAcylation ¿ and phosphorylation-dependent signal transduction pathway in cancer, which will result in development of O-GlcNAcylation-inducing anti-cancer drugs.