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不均一核核糖核蛋白B1通过抑制DNA依赖性蛋白激酶活性来损害DNA修复。

Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity.

作者信息

Iwanaga Kentaro, Sueoka Naoko, Sato Akemi, Hayashi Shinichiro, Sueoka Eisaburo

机构信息

Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.

出版信息

Biochem Biophys Res Commun. 2005 Aug 5;333(3):888-95. doi: 10.1016/j.bbrc.2005.05.180.

Abstract

Heterogeneous nuclear ribonucleoprotein B1, an RNA binding protein, is overexpressed from the early stage of lung cancers; it is evident even in bronchial dysplasia, a premalignant lesion. We evaluated the proteins bound with hnRNP B1 and found that hnRNP B1 interacted with DNA-dependent protein kinase (DNA-PK) complex, and recombinant hnRNP B1 protein dose-dependently inhibited DNA-PK activity in vitro. To test the effect of hnRNP B1 on DNA repair, we performed comet assay after irradiation, using normal human bronchial epithelial (HBE) cells treated with siRNA for hnRNP A2/B1: reduction of hnRNP B1 treated with siRNA for hnRNP A2/B1 induced faster DNA repair in normal HBE cells. Considering these results, we assume that overexpression of hnRNP B1 occurring in the early stage of carcinogenesis inhibits DNA-PK activity, resulting in subsequent accumulation of erroneous rejoining of DNA double-strand breaks, causing tumor progression.

摘要

异质性细胞核核糖核蛋白B1是一种RNA结合蛋白,在肺癌早期即过度表达;在癌前病变支气管发育异常中也很明显。我们评估了与hnRNP B1结合的蛋白质,发现hnRNP B1与DNA依赖性蛋白激酶(DNA-PK)复合物相互作用,并且重组hnRNP B1蛋白在体外剂量依赖性地抑制DNA-PK活性。为了测试hnRNP B1对DNA修复的影响,我们在用针对hnRNP A2/B1的siRNA处理的正常人支气管上皮(HBE)细胞中进行照射后进行彗星试验:用针对hnRNP A2/B1的siRNA处理后hnRNP B1的减少在正常HBE细胞中诱导更快的DNA修复。考虑到这些结果,我们推测在癌变早期发生的hnRNP B1过表达会抑制DNA-PK活性,导致随后DNA双链断裂错误重新连接的积累,从而导致肿瘤进展。

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