有助治疗卡波氏肉瘤新药的新进展

导读：英国研究人员日前报告说，他们发现了相关蛋白质在卡波氏肉瘤病毒复制中的相互作用，这将有助于研发治疗卡波氏肉瘤新药。

英国研究人员日前报告说，他们发现了相关蛋白质在卡波氏肉瘤病毒复制中的相互作用，这将有助于研发治疗卡波氏肉瘤新药。

英国利兹大学研究人员在新一期《欧洲分子生物学组织期刊》（The  EMBO  Journal）上报告说，他们发现，引发卡波氏肉瘤的病毒在入侵人体时会指导合成一种名为ORF57的蛋白质，这种蛋白质与一种PYM蛋白质相互作用，使病毒得以复制。如果在实验中阻止这两种蛋白质之间反应，病毒就不能进行复制和扩散。

研究人员怀特豪斯说，这是首次发现相关蛋白质在卡波氏肉瘤病毒复制中的作用，有望在此基础上研发阻止病毒复制的新药，进而有效治疗这种癌症。

卡波氏肉瘤又名多发性出血性肉瘤，是一种血管肿瘤导致的癌症。它多发于免疫系统受损人群，如艾滋病患者等。目前化疗等手段对这种癌症效果不彰，且常有副作用。（生 物 谷Bioon.com）

Bioon.com推荐原文出处：

The EMBO Journal  doi:10.1038/emboj.2010.77

Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs
James R Boyne1,3,4, Brian R Jackson1,4, Adam Taylor1, Stuart A Macnab1 and Adrian Whitehouse1,2

1 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
2 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK
3 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK

Kaposi's sarcoma-associated herpesvirus (KSHV) expresses numerous intronless mRNAs that are unable to access splicing-dependent cellular mRNA nuclear export pathways. To circumvent this problem, KSHV encodes the open reading frame 57 (ORF57) protein, which orchestrates the formation of an export-competent virus ribonucleoprotein particle comprising the nuclear export complex hTREX, but not the exon-junction complex (EJC). Interestingly, EJCs stimulate mRNA translation, which raises the intriguing question of how intronless KSHV transcripts are efficiently translated. Herein, we show that ORF57 associates with components of the 48S pre-initiation complex and co-sediments with the 40S ribosomal subunits. Strikingly, we observed a direct interaction between ORF57 and PYM, a cellular protein that enhances translation by recruiting the 48S pre-initiation complex to newly exported mRNAs, through an interaction with the EJC. Moreover, detailed biochemical analysis suggests that ORF57 recruits PYM to intronless KSHV mRNA and PYM then facilitates the association of ORF57 and the cellular translation machinery. We, therefore, propose a model whereby ORF57 interacts directly with PYM to enhance translation of intronless KSHV transcripts.