Significance of hnRNP A2/B1 proteins in lung cancer

杂源核核糖核蛋白(HnRNP)A2/B1是参与前RNA加工的核RNA结合蛋白。已有研究表明，A2/B1的过度表达有助于肿瘤的早期发现。首先，我们用合成的多肽作为免疫原，制备了抗A2的单抗4G8。我们研制的包括4G8在内的抗A2/B1单抗能够分别识别A2和B1，其特异性为研究A2和B1的生化和功能特性奠定了基础。这些抗体表明A2和B1在细胞内的分布和通过细胞周期的代谢是不同的。A2/B1蛋白被报道与DNA重复序列结合。与A2和BOA相比，B1和B0b对端粒单链DNA(SsDNA)具有更高的亲和力。用纯化的B1和B0b进行的动力学分析表明，它们与单一的三聚体重复序列相互作用。功能分析表明，B1和B0b以串联方式与三聚体重复序列结合，保护它们免受核酸酶的攻击，并促进端粒酶活性。转基因小鼠的呼吸系统没有任何变化，但发现小鼠精子发生异常。因此，我们将研究hnRNP A2/B1与异常的关系。

Hetrogenous nuclear ribonucleoprotein (hnRNP) A2/B1 are nuclear RNA binding proteins involved in pre-RNA processing. It has been reported that the overexpression, of A2/B1, is useful for detecting cancers in early stage. First, we generated an anti-A2 monoclonal antibody 4G8 using the synthetic peptide as an immunogen. Our original anti-A2/B1 monoclonal antibodies including 4G8 could separately recognized A2 and B1, and their specificity made them useful in the study of the biochemical and functional properties of A2 and B1. These antibodies have demonstrated differences between A2 and B1 in the intracellular distribution and in the metabolism through cell cycles.A2/B1 proteins have been reported to bind teromeric DNA repeats. B1 and B0b, which is one of the minor isoforms of B1, were suggested to have higher affinities to telomeric single-strand DNA (ssDNA) than A2 and BOa. Kinetic analyses using purified B1 and B0b indicated that they interact with a single array of teromeric repeats. Functional assays demonstrated that B1 and B0b bind with teromeric repeats in a tandem fashion and protect them from a nuclease and promote telomerase activity.Transgenic mice did not show any changes in respiratory system, however, spermatogenetic abnormality was found in the mice. Therefore, we will research the relationship between hnRNP A2/B1 and the abnormality.