GLYCOPROTEINS IN NORMAL & LEUKEMIC CELL DIFFERENTIATION

这项建议的主要目的是比较膜 正常人(髓系细胞和淋巴系细胞)与非霍奇金淋巴瘤细胞的分化 肿瘤细胞，并了解碳水化合物和 人类白细胞分化中的糖蛋白。 我们已经证明，白细胞上的一种主要唾液酸糖蛋白--白唾液素， 在T细胞过程中其O-糖链的结构发生了显著变化 分化与白血病和免疫缺陷有关。我们还有 分离出白唾液素的cDNA和基因组DNA并鉴定出一个新的 负责白唾液酸蛋白表达的启动子序列 吉恩。进一步的研究将阐明O-葡聚糖在 分离与胸腺细胞凝集素结合的胸腺细胞发育 O-葡聚糖的未成熟形式和评估O-葡聚糖的作用 唾液酸化在髓系细胞分化中的作用此外，我们还将 阐明独特的细胞类型特异性表达的机制 白涎素通过鉴定转录因子(S)增强或 根据单元格类型，取消其表达。转基因小鼠将 也可用于检测白唾液素基因的异位表达 扰乱发展。 我们鉴定了GalBeta1&gt；44GlcNAc(GlcNAc To Gal)Beta&gt；3-N-乙酰基葡萄糖- 氨基转移酶--生物合成的关键酶 与细胞-细胞密切相关的聚乳糖胺多聚糖 正常和致癌条件下的相互作用。进一步研究 将克隆β1和3-N-乙酰氨基葡萄糖转移酶的cDNA 并确定这种转移酶的废除如何影响器官和 转基因小鼠的组织形成和拟胚体的形成 胚胎干细胞。 建议的研究将使我们能够提供关键信息 含特定碳水化合物和糖蛋白的表达 这些碳水化合物控制着分化和发育。在……里面 为了实现这一目标，我们将全力以赴 碳水化合物生物化学、分子生物学和细胞生物学 在过去。

The primary object of this proposal is to compare the membrane differentiation of normal (myeloid and lymphoid cells) with that of tumor cells, and to understand the role of carbohydrates and glycoproteins in human leukocyte differentiation. We have shown that leukosialin, a major sialoglycoprotein on leukocytes, exhibits a dramatic structural change in its O-glycans during T-cell differentiation and in leukemia and immunodeficiency. We have also isolated cDNAs and genomic DNA for leukosialin and identified a novel promoter sequence responsible for the expression of the leukosialin gene. Further studies will be to elucidate the role of O-glycans in thymocyte development by isolating thymocyte lectin that binds to immature forms of the O-glycans and to assess the role of O-glycan sialylation in myeloid cell differentiation. In addition, we will elucidate the mechanisms of unique cell type-specific expression of leukosialin by identifying the transcription factor(s) which enhance or suppress its expression, depending on cell types. Transgenic mice will also be utilized to test if ectopic expression of leukosialin gene perturbs development. We identified GalBeta1> 44GlcNAc (GlcNAc to Gal) Beta> 3-N-acetylglucos- aminyltransferase as the key enzyme in the biosynthesis of polylactosaminoglycans which are critically involved in cell-cell interaction under normal and tumorigenic conditions. Further studies will be to clone cDNAs for the Beta1> 3-N-acetylglucosaminyltransferase and determine how the abolishment of this transferase affects organ and tissue formation in transgenic mice and embryoid body formation by embryonic stem cells. The studies proposed will enable us to provide critical information how the expression of specific carbohydrates and glycoproteins containing these carbohydrates control the differentiation and development. In order to achieve this goal, we will draw all our strength in carbohydrate biochemistry, molecular biology, and cell biology, gained in the past.