Antibodies to O-GlcNAc modified histones for chromatin biology and epigenetic res

描述（由申请人提供）：核蛋白和细胞质蛋白的o -糖基化- n -乙酰- d -氨基葡萄糖片段（O-GlcNAc）是一种常见的翻译后修饰，在细胞刺激下具有高度动态和波动。到目前为止，这种类型的糖基化已经在大约1000种人类蛋白质中被发现，并且被认为几乎与蛋白质磷酸化一样广泛和丰富。事实上，O-GlcNAc经常与蛋白磷酸化发生竞争，这两种修饰在信号传导、转录以及癌基因和肿瘤抑制基因的功能调节中存在广泛的串扰。这种修饰似乎在包括癌症、阿尔茨海默病和糖尿病在内的关键病理生理条件中起着重要作用。

DESCRIPTION (provided by applicant): O-glycosylation of nuclear and cytoplasmic proteins by a single ?-N-acetyl-D-glucosamine moiety (O-GlcNAc) is a common post-translational modification that is highly dynamic and fluctuates in response to cellular stimuli. This type of glycosylation has been found on approximately a thousand human proteins to date, and is thought to be nearly as wide-spread and abundant as protein phosphorylation. In fact, O-GlcNAc often competes with protein phosphorylation, and these two modifications have extensive crosstalk in the regulation of signaling, transcription, and the functions of oncogenes and tumor suppressors. The modification appears to play a major role in key pathophysiological conditions including cancer, Alzheimer's disease, and diabetes. Some of the first proteins identified carrying this modification were transcription factors, and it has become clear in the last several years that O-GlcNAc plays a major role in chromatin remodeling and gene expression. The focus of this proposal is to develop site-specific antibodies that can be used as tools in the elucidation of the role that O-GlcNAc plays in epigenetics. We will utilize a new immunogen strategy to develop site-specific O-GlcNac antibodies to five sites of O-GlcNAc modification on the four histone proteins, all of which play a role in chromatin modeling and epigenetics. Consequently, if we are successful, the mAbs generated in this initial study will have an immediate impact on epigenetic research and could have far reaching implications in disease research.