Y box-binding protein-1 binds preferentially to single-stranded nucleic acids and exhibits 3'-->5' exonuclease activity

We have previously shown that Y box-binding protein-1 (YB-1) binds preferentially to cisplatin-modified Y box sequences. Based on structural and biochemical data, we predicted that this protein binds single-stranded nucleic acids. In the present study we confirmed the prediction and also discovered some unexpected functional features of YB-1. We found that the cold shock domain of the protein is necessary but not sufficient for double-stranded DNA binding while the C-tail domain interacts with both single-stranded DNA and RNA independently of the cold shock domain. In an in vitro translation system the C-tail domain of the protein inhibited translation but the cold shock domain did not. Both in vitro pull-down and in vivo co-immunoprecipitation assays revealed that YB-1 can form a homodimer. Deletion analysis mapped the C-tail domain of the protein as the region of homodimerization. We also characterized an intrinsic 3′→5′ DNA exonuclease activity of the protein. The region between residues 51 and 205 of its 324-amino acid extent is required for full exonuclease activity. Our findings suggest that YB-1 functions in regulating DNA/RNA transactions and that these actions involve different domains.     

Y-box结合蛋白功能及对肿瘤发生的影响

Y-box结合蛋白家族成员是一类高度保守的顺式作用元件, 广泛存在于原核及真核生物细胞中。它是一种多功能蛋白, 与转录调节、翻译调控、mRNA选择性剪接、DNA的修复、细胞增殖和再生等有关。Y-box结合蛋白的氨基酸序列包含3个结构域: 氨基酸N末端, 亲水结构域C末端, 冷休克结构域(cold shock domain CSD), 保守的冷休克结构域决定了Y-box结合蛋白的大部分功能。最近研究发现, 定位于细胞核中的YB-1蛋白在局部晚期非小细胞肺癌的预防上可作为新的靶位点, YB-1蛋白还可通过对抑癌基因p53启动子抑制起负调控作用, 此外, YB-1蛋白在PI3K/Akt信号通路中也起到重要的作用, 这些研究都为肿瘤的治疗提供了新的线索和启示。文章就Y-box结合蛋白功能及其对肿瘤发生的影响等方面进行概述。     

Nonspecific and specific interactions of Y-box-binding protein 1 (YB-1) with mRNA and posttranscriptional regulation of protein synthesis in animal cells

Y-box-binding protein 1 (YB-1) is an animal multifunctional DNA/RNA-binding protein that is involved in reproduction, storing, and expression of genetic information. YB-1 accompanies mRNA throughout its life, from synthesis to degradation, and has a high specific and nonspecific affinity for RNA. In the nucleus YB-1 regulates mRNA processing. In the cytoplasm YB-1 is responsible for global and selective regulation of protein synthesis, as well as the mRNA life. This review focuses on the role of YB-1 in regulating translation. The possible mechanisms of the positive and negative effects of YB-1 on this process are considered. The recent original data are described, supporting the role of YB-1 as a major structural component of mRNP. Data about specific interactions of YB-1 with RNA are summarized for the first time.     

YB-1与肿瘤发生及治疗

Y-box结合蛋白(Y-box binding protein,YB)是一类广泛存在于从低等到高等多种生物中的蛋白质家族,在体内行使多种生物学功能.大量研究表明,YB-1作为该家族成员之一,与许多重要的生物大分子存在密切联系,并对细胞、组织和机体的生理机能产生重大影响.更为重要的是,YB-1在多种疾病,尤其是恶性肿瘤的发生和发展中也起到十分关键的作用,对癌细胞表型的维持及肿瘤多药耐药性(MDR)的产生具有全方位的影响.以YB-1为作用靶点的新型肿瘤治疗策略可望有效控制癌症患者病情恶化,改善耐药状况.现就对YB-1与肿瘤发生和发展之间关系的研究进展,以及针对YB-1治疗策略的制定作一评述和展望.