Elucidating the regulation and function of the cell-cycle regulator RGC-32 in Epstein-Barr virus transformed cells

阐明细胞周期调节剂 RGC-32 在 Epstein-Barr 病毒转化细胞中的调节和功能

• 批准号: MR/K01952X/1
• 负责人: Michelle West
• 金额: $ 66.01万
• 依托单位: University of Sussex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK01952X%2F1
• 关键词: Elucidating; regulation; function; cell; cycle

We have discovered that a key human gene implicated in many cancers (RGC-32) is highly regulated at the level of both RNA and protein production in white blood cells infected with the cancer-associated virus Epstein-Barr virus (EBV). The high expression of this protein may therefore play a role in the development of cancers associated with EBV infection that include Burkitt's lymphoma, Hodgkin's disease, post-transplant lymphoma and nasopharyngeal carcinoma. Our research aims to obtain further information on how RGC-32 regulates growth and how its expression can be controlled by cellular and viral proteins. This research will therefore increase our understanding of how overproduction of RGC-32 may contribute to cancer development.Specifically we will determine:1. How EBV proteins and cellular factors regulate RGC-32 RNA expression in EBV-infected cells.2. How short RNA molecules (microRNAs) and RNA binding proteins control RGC-32 protein production.3. How RGC-32 controls cell growth.Our research will provide important information for basic scientists and clinicians working in the fields of cancer research and treatment. The long term beneficiaries of this research could therefore include patients suffering from diseases in which RGC-32 expression is altered.

我们发现，在感染了癌症相关病毒eb病毒（EBV）的白细胞中，一个与许多癌症有关的关键人类基因（RGC-32）在RNA和蛋白质生产水平上受到高度调控。因此，这种蛋白的高表达可能在EBV感染相关癌症的发展中发挥作用，包括伯基特淋巴瘤、霍奇金病、移植后淋巴瘤和鼻咽癌。我们的研究旨在进一步了解RGC-32如何调节生长及其表达如何受到细胞和病毒蛋白的控制。因此，这项研究将增加我们对过量生产RGC-32如何促进癌症发展的理解。具体来说，我们将确定：1。EBV蛋白和细胞因子如何调控感染细胞的RGC-32 RNA表达。短RNA分子（microRNAs）和RNA结合蛋白如何控制RGC-32蛋白的产生。RGC-32如何控制细胞生长。我们的研究将为从事癌症研究和治疗领域的基础科学家和临床医生提供重要信息。因此，这项研究的长期受益者可能包括患有RGC-32表达改变的疾病的患者。

项目成果

Enhancer Control of MicroRNA miR-155 Expression in Epstein-Barr Virus-Infected B Cells.

• DOI: 10.1128/jvi.00716-18
• 发表时间: 2018-10-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Wood CD;Carvell T;Gunnell A;Ojeniyi OO;Osborne C;West MJ
• 通讯作者: West MJ

Pumilio directs deadenylation-associated translational repression of the cyclin-dependent kinase 1 activator RGC-32.

• DOI: 10.1093/nar/gky038
• 发表时间: 2018-04-20
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Brocard M;Khasnis S;Wood CD;Shannon-Lowe C;West MJ
• 通讯作者: West MJ

RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth.

• DOI: 10.1093/nar/gkw085
• 发表时间: 2016-06-02
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Gunnell A;Webb HM;Wood CD;McClellan MJ;Wichaidit B;Kempkes B;Jenner RG;Osborne C;Farrell PJ;West MJ
• 通讯作者: West MJ

Enhancer control of miR-155 expression in Epstein-Barr virus infected B cells

• DOI: 10.1101/311886
• 发表时间: 2018-05
• 期刊: bioRxiv
• 作者: C. David Wood;Thomas Carvell;Andrea Gunnell;Opeoluwa O. Ojeniyi;Cameron S. Osborne;M. West

Chromatin reorganisation in Epstein-Barr virus-infected cells and its role in cancer development.

• DOI: 10.1016/j.coviro.2017.08.004
• 发表时间: 2017-10
• 期刊: Current opinion in virology
• 影响因子: 5.9
• 作者: M. West