Purα:: a multifunctional single-stranded DNA- and RNA-binding protein

Purα:: a multifunctional single-stranded DNA- and RNA-binding protein
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DOI:
10.1093/nar/28.17.3197
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发表时间:
2000-09-01
影响因子:
14.9
通讯作者:
Khalili, K
Khalili, K
中科院分区:
生物学2区
文献类型:
--
作者:
Gallia, GL;Johnson, EM;Khalili, K

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Pur alpha是一种普遍存在的序列特异性DNA和RNA结合蛋白,在真核细胞中高度保守。Pur alpha参与多种细胞功能,包括转录激活和抑制、翻译和细胞生长。此外,该蛋白质已显示参与调节在中枢神经系统(CNS)中复制的几种人病毒,包括人免疫缺陷病毒I型(HIV-1)和JC病毒(JCV)。Pur α通过与细胞蛋白质相互作用发挥其部分活性,所述细胞蛋白质包括pRb、E2F、细胞周期蛋白A、Spl和Y-盒蛋白质家族的成员,包括YB-1和MSY 1,以及病毒蛋白如多瘤病毒大T抗原和HIV-1达特。Pur α与其靶DNA序列相互作用以及与几种病毒和细胞蛋白质缔合的能力受RNA调节。Pureer也被证明参与细胞生长和增殖。它与pRb,E2F和细胞周期蛋白A的关联加上其在整个细胞周期中的波动水平,将Pur α定位为细胞周期中的关键因子。此外,显微注射研究表明,Pur alpha导致G(1)或G(2)阻滞,这取决于注射的细胞周期时间。编码Pur α的基因已定位于在骨髓性白血病和其它癌症中经常缺失的人类基因座,并且在许多淋巴癌病例中已检测到Pur α基因缺失。以下综述详细介绍了Pur alpha的结构特征、其家族成员以及该蛋白参与调节各种细胞和病毒基因、病毒复制和细胞生长。
Pur alpha is a ubiquitous, sequence-specific DNA- and RNA binding protein which is highly conserved in eukaryotic cells. Pur alpha has been implicated in diverse cellular functions, including transcriptional activation and repression, translation and cell growth. Moreover, this protein has been shown to be involved in regulating several human viruses which replicate in the central nervous system (CNS), including human immunodeficiency virus type I (HIV-1) and JC virus (JCV), Pur alpha exerts part of its activity by interacting with cellular proteins, including pRb, E2F, cyclin A, Spl and members of the Y-box family of proteins, including YB-1 and MSY1, as well as viral proteins such as polyomavirus large T-antigen and HIV-1 Tat. The ability of Pur alpha to interact with its target DNA sequence and to associate with several viral and cellular proteins is modulated by RNA. Purer has also been shown to be involved in cell growth and proliferation. Its association with pRb, E2F and cyclin A coupled with its fluctuating levels throughout the cell cycle, position Pur alpha as a crucial factor in the cell cycle. Moreover, microinjection studies demonstrate that Pur alpha causes either a G(1) or G(2) arrest depending on the cell cycle time of injection. The gene encoding Pur alpha has been localized to a human locus which is frequently deleted in myelogenous leukemias and other cancers and Pur alpha gene deletions have been detected in many cases of lymphoid cancers. The following review details the structural characteristics of Pur alpha, its family members and the involvement of this protein in regulating various cellular and viral genes, viral replication and cell growth.