Molecular identification of a sialyl 9-O-acetyl transferase

唾液酸9-O-乙酰基转移酶的分子鉴定

• 批准号: 7371081
• 负责人: SHIV Subramaniam PILLAI
• 金额: $ 21.46万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371081
• 关键词: Acetylation; Allergic; Autoimmune Diseases; Autoimmune Process; B-Lymphocytes; Biological Assay; CD22 gene; Candidate Disease Gene; Cells; Code; Deacetylation; Development; Disease; Employee Strikes; Enzymes; Event; Family; Genes; Health; Immune; Immune response; Immune system; Libraries; Link; Lupus; Lymphocyte; Molecular; Polysaccharides; Positioning Attribute; RNA Interference; Receptors, Antigen, B-Cell; Regulation; Risk; Sialic Acids; Therapeutic Intervention; Transferase; base; esterase; in vivo; novel; receptor; response; sialic acid binding Ig-like lectin; small hairpin RNA

DESCRIPTION (provided by applicant): Acetylation and deacetylation of the 9-OH position of sialic acid may serve as a rheostat controlling the strength of B cell antigen receptor responses in vivo, by modulating the activity of CD22, an inhibitory receptor of the Siglec family. Acetylation of sialic acid regulates other Siglecs and may potentially influence other aspects of immune regulation in immune cells other than B lymphocytes. The enzymes that regulate these acetylation and deacetylation events are potentially important targets for therapeutic intervention in immunological disorders, particularly humoral autoimmune disorders. Although the identity of the sialyl 9-O-acetyl esterase has been established and the consequences of the loss of this enzyme have been examined, the crucial sialyl 9-0-acetyl transferase remains to be characterized and cloned. We plan to utilize a cell-based assay to identify and characterize this sialyl 9-O-acetyl transferase. This cell-based assay will be used in conjunction with post-transcriptional gene silencing to identify genes that contribute to 9-O-acetylation of sialic acid. Lentiviral shRNA libraries will be used for both a candidate gene knockdown approach followed by an arrayed library strategy if necessary. The sialyl 9-O-acetyl transferase is a potential modulator of important inhibitory receptors in the immune system. Identifying and characterizing this enzyme may provide an important and novel target for the therapy of autoimmune and allergic disorders. The gene that codes for an enzyme that controls the strength of the immune response will be studied. This gene may be an important target for the treatment of lupus and other related diseases.

描述（申请人提供）：唾液酸 9-OH 位的乙酰化和脱乙酰化可作为变阻器，通过调节 Siglec 家族的抑制性受体 CD22 的活性来控制体内 B 细胞抗原受体反应的强度。唾液酸的乙酰化可调节其他 Siglec，并可能影响 B 淋巴细胞以外的免疫细胞中免疫调节的其他方面。调节这些乙酰化和脱乙酰化事件的酶是免疫性疾病，特别是体液自身免疫性疾病的治疗干预的潜在重要靶标。尽管唾液酸 9-O-乙酰酯酶的身份已经确定，并且已经检查了该酶丢失的后果，但关键的唾液酸 9-0-乙酰转移酶仍有待表征和克隆。我们计划利用基于细胞的测定来识别和表征这种唾液酸 9-O-乙酰基转移酶。这种基于细胞的测定将与转录后基因沉默结合使用，以鉴定有助于唾液酸 9-O-乙酰化的基因。慢病毒 shRNA 文库将用于候选基因敲低方法，如有必要，还可用于阵列文库策略。唾液酸 9-O-乙酰基转移酶是免疫系统中重要抑制性受体的潜在调节剂。识别和表征这种酶可能为自身免疫和过敏性疾病的治疗提供重要且新颖的靶点。将研究编码控制免疫反应强度的酶的基因。该基因可能是治疗狼疮和其他相关疾病的重要靶点。