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作 者:张玮玮[1] 黄惠芳[1] 李庆伟[1] 马飞[1]
机构地区:[1]辽宁师范大学海洋生物功能基因与蛋白质组学研究所,大连116029
出 处:《遗传》2006年第9期1153-1160,共8页Hereditas(Beijing)
基 金:国家自然科学基金(编号:60305001);福建省自然科学基金(编号:D0410003);辽宁省教育厅青年基金(编号:2004F090);大连市优秀青年科技人才基金项目资助~~
摘 要: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(coldshockdomainCSD),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。Y-box binding proteins, belonging to a family of multifunctional proteins conserved from bacteria to human, are involved in transcriptional and translational regulation of various genes, mRNA alternative splicing, DNA replication and repair, as well as cell proliferation. A typical Y-box binding protein contains three structure domains, namely the N-terminal domain, the hydrophilic C-terminal domain and the conserved cold shock domain (CSD) which binds strongly to inverted CCAAT box found in different promoters and determines protein function.Y-box binding proteins may play an important physiological role in cell proliferation.For example, the human Y-box protein 1 (YB-1) may be repressed in the oncogenic phosphoinosit[de 3-kinase (PI3K) pathway. In addition, it may also act as a negative regulator of p53. It has been demonstrated that YB-1 represses transcription of the p53 promoter in a sequence-specific manner using specifically reporter assays. This implies that YB-1 may, in some situations, protect cells from p53-med[ated apoptosis, indicating that YB-1 may be a good target for the development of a new therapeutics.The function of Y-box binding protein and its effect on carcinogenesis are summarized in the paper. We hope to further explore the functional roles of Y-box binding protein, and provide some helpful lines and suggestions for tumor control.
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