A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma.
A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma.
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DOI：
10.1084/jem.189.7.1101
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发表时间：
1999-04-05
期刊：
影响因子：
--
通讯作者：
Tan EM
中科院分区：
文献类型：
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作者：
Zhang JY;Chan EK;Peng XX;Tan EM
在肝细胞癌（HCC）中，在30-40%的患者中检测到针对细胞内抗原的自身抗体。患有慢性肝炎或肝硬化的患者发展为HCC，当这种情况发生时，一些患者表现出新特异性的自身抗体。有人认为，这些新的自身抗体反应可能是免疫系统对参与转化相关细胞事件的蛋白质的反应。用一份显示含有未鉴定细胞抗原的抗体的HCC血清对cDNA表达文库进行免疫筛选，并分离出全长cDNA克隆，其开放阅读框编码556个氨基酸，预测分子量为62 kD。62-kD蛋白含有两种类型的RNA结合基序，即共有序列RNA结合结构域（CS-RBD）和四个hnRNP K同源结构域（KH）。该蛋白质暂时称为p62，在氨基酸序列水平上与其他三种蛋白质具有接近的同一性（66-70%），并且所有四种蛋白质可能属于在NH 2-末端区域具有CS-RBD和在中间至COOH-末端区域具有四个KH结构域的家族。同源蛋白质是：在癌症中过表达的含有KH结构域的蛋白质（Koc）; zipcode结合蛋白，一种结合鸡β-肌动蛋白mRNA中的保守核苷酸元件的蛋白质（ZBP 1）;和一种结合非洲爪蟾TFIIIA基因中的启动子顺式元件的蛋白质（B3）。p62蛋白位于细胞质中，在21%的HCC患者队列中发现了自身抗体。慢性肝炎和肝硬化患者，这些疾病是HCC的常见前体，对这些自身抗体呈阴性，表明免疫反应可能与导致转化的细胞事件有关。然而，p62自身抗原作为转化过程中的一个因素的可能参与仍有待阐明。
In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens are detected in 30–40% of patients. Patients with chronic hepatitis or liver cirrhosis develop HCC, and when this occurs, some patients exhibit autoantibodies of new specificities. It has been suggested that these novel autoantibody responses may be immune system reactions to proteins involved in transformation-associated cellular events. One HCC serum shown to contain antibodies to unidentified cellular antigens was used to immunoscreen a cDNA expression library, and a full length cDNA clone was isolated with an open reading frame encoding 556 amino acids with a predicted molecular mass of 62 kD. The 62-kD protein contained two types of RNA-binding motifs, the consensus sequence RNA–binding domain (CS-RBD) and four hnRNP K homology (KH) domains. This protein, provisionally called p62, has close identity (66–70%) to three other proteins at the amino acid sequence level, and all four proteins may belong to a family having CS-RBD in the NH2-terminal region and four KH domains in the mid-to-COOH– terminal region. The homologous proteins are: KH domain–containing protein overexpressed in cancer (Koc); zipcode binding protein, a protein which binds to a conserved nucleotide element in chicken β-actin mRNA (ZBP1); and a protein which binds to a promoter cis element in Xenopus laevis TFIIIA gene (B3). p62 protein is cytoplasmic in location, and autoantibodies were found in 21% of a cohort of HCC patients. Patients with chronic hepatitis and liver cirrhosis, conditions which are frequent precursors to HCC, were negative for these autoantibodies, suggesting that the immune response might be related to cellular events leading to transformation. However, the possible involvement of p62 autoantigen as a factor in the transformation process remains to be elucidated.