CHARACTERIZATION OF A NEW RETINAL AUTOANTIGEN GENE CORRESPONDING WITH CANCER-ASSOCIATED RETINOPATHY

与癌症相关视网膜病变相对应的新视网膜自身抗原基因的特征

• 批准号: 13671829
• 负责人: KIKUCHI Takanobu
• 金额: $ 2.3万
• 依托单位: SHINSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671829/
• 关键词: Cancer-associated retinopathy; autoantibody; retinal antigen; PTB-like protein; RNA binding protein; 抗原決定部位; RNA結合タンパク; PTBLP遺伝子

(1) Human homologue of polypyrimidine tract binding protein (PTB), a possible autoantigen for cancer-associated retinopathy (CAR), was isolated from a human retinal cDNA library. This homologue, named PTB-like protein (PTBLP), encodes a 532 amino acid residue protein and has four RNA recognition motifs (RRMs). The third and fourth RRMs are required for RNA binding ability. CAR serum recognized the PTBLP, the antigenic determinant of the PTBLP was localized within 12 amino acids of the C-terminal region. The sequence of the peptide was included in the fourth RRM sequence. Autoantibodies in the sera of the patients with paraneoplastic neurologic disorders react to a variety of neuron specific proteins. These proteins can be classified into three groups : (1) cell surface protein, e.g., voltage-gated calcium channels, (2) cytosolic proteins, e.g., recoverin and TULP1 ; and (3) nuclear RNA binding proteins, e.g., Hu-family proteins containing RRM domain and NOVA protein containing KH domai … More n. The PTBLP is a new member of the third group. This study expands the understanding of the pathogenesis of paraneoplastic disorders with antibodies against neuronal RNA binding proteins.(2) We have studied whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of NGF-induced neuronal differentiation of PC12 cells, PTBLP-L (long form containing four RRMs) was down-regulated whereas PTBLP-S (short form containing only two RRMs in the N-terminal region) was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L. Less

(1) 从人类视网膜 cDNA 文库中分离出人类多聚嘧啶束结合蛋白 (PTB) 同源物，该蛋白可能是癌症相关视网膜病 (CAR) 的自身抗原。这种同源物被命名为 PTB 样蛋白 (PTBLP)，编码一个 532 个氨基酸残基的蛋白，并具有四个 RNA 识别基序 (RRM)。第三和第四个 RRM 是 RNA 结合能力所必需的。 CAR血清识别PTBLP，PTBLP的抗原决定簇位于C端区域的12个氨基酸内。该肽的序列包含在第四个RRM序列中。副肿瘤性神经系统疾病患者血清中的自身抗体会对多种神经元特异性蛋白质产生反应。这些蛋白质可分为三组：(1)细胞表面蛋白质，例如电压门控钙通道，(2)胞质蛋白质，例如恢复蛋白和TULP1； (3)核RNA结合蛋白，例如含有RRM结构域的Hu家族蛋白和含有KH结构域的NOVA蛋白……更多n。 PTBLP是第三组的新成员。这项研究利用针对神经元RNA结合蛋白的抗体扩展了对副肿瘤性疾病发病机制的理解。(2)我们使用PC12细胞研究了PTBLP是否在神经元分化中发挥作用。在 NGF 诱导 PC12 细胞神经元分化的过程中，PTBLP-L（包含四个 RRM 的长型）下调，而 PTBLP-S（N 端区域仅包含两个 RRM 的短型）上调。将 PTBLP-L 转染到 PC12 细胞中导致神经元分化受到抑制。然而，在 PTBLP-S 转染的细胞中，这种抑制并不明显。当PTBLP-L和PTBLP-S共转染时，PTBLP-L的抑制作用下降。在分化细胞中，PTBLP-S 定位于细胞核，而 PTBLP-L 分散在整个细胞质和神经元生长锥中。这些发现表明 PTBLP-L 作为神经元分化的负调节因子，而 PTBLP-S 作为 PTBLP-L 的竞争者。较少的

项目成果

Ichikawa M, Kikuchi T, Tateiwa H, et al.: "Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells"J.Biochem.. 131. 861-868 (2002)

Ichikawa M、Kikuchi T、Tateiwa H 等人：“PTB 样蛋白（一种神经元 RNA 结合蛋白）在 PC12 细胞分化过程中的作用”J.Biochem.. 131. 861-868 (2002)

Hisashi Tateiwa, et. al: "Molecular cloning and characterization of human PTB-like protein : a possible retinal autoantigen of cancer-associated retinopathy"Journal of Neuroimmunology. 120. 161-169 (2001)

立岩恒，等。

Tateiwa H, Gotoh N, Ichikawa M, Kikuchi T, Yoshimura N.: "Molecular cloning and characterization of human PTB-like protein : a possible retinal autoantigen of cancer-associated retinopathy"J.Neuroimmunol.. 120. 161-169 (2001)

Tateiwa H、Gotoh N、Ichikawa M、Kikuchi T、Yoshimura N.：“人 PTB 样蛋白的分子克隆和表征：癌症相关视网膜病变的可能视网膜自身抗原”J.Neuroimmunol.. 120. 161-169 (2001

Ichikawa M, Kikuchi T, Tateiwa H, et al.: "Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC 12 cells"J. Biochem.. 131. 861-868 (2002)

Ichikawa M、Kikuchi T、Tateiwa H 等人：“PTB 样蛋白（一种神经元 RNA 结合蛋白）在 PC 12 细胞分化过程中的作用”J.