YB-1 Synthesis Is Regulated by mTOR Signaling Pathway

YB-1 is a eukaryotic protein with numerous intra- and extracellular functions based on its ability to interact with RNA, DNA, and many proteins. In spite of achievements in studying its functions, regulation of YB-1 synthesis in the cell remains poorly understood. In the current study Western and Northern blotting were used to determine the amounts of YB-1 and YB-1 mRNA in rabbit organs and several cell lines. As found, in the majority of studied eukaryotic cells a considerable proportion of YB-1 mRNA was stored in free mRNPs, i.e., was poorly translated. Also, we demonstrated that YB-1 synthesis depended on conditions that determined the rate of cell division. Specific suppression of YB-1 synthesis resulted from inhibition of the mTOR signaling pathway with inhibitor PP242, but not rapamycin. Experiments on reporter constructs showed that dependence of YB-1 mRNA translation on activity of the mTOR signaling pathway was dictated by 5′ untranslated regions of this mRNA, irrelatively of the TOP-like sequences at the beginning of 5′ UTR.     

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.