Tumour virus deregulation of the cell cycle: translational control and function of RGC-32

肿瘤病毒对细胞周期的失调：RGC-32的翻译控制和功能

• 批准号: MR/S009620/1
• 负责人: Michelle West
• 金额: $ 84.33万
• 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: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS009620%2F1
• 关键词: Tumour; virus; deregulation; cell; cycle

We have been studying a human protein (RGC-32) that may be involved in the development of many cancers. We found that RGC-32 is produced when white blood cells are infected by the cancer virus Epstein-Barr virus, suggesting that RGC-32 may be involved in Epstein-Barr virus-associated cancers. These include many lymphomas e.g. Burkitt's, Hodgkin's and post-transplant lymphoma. We have shown that if we reduce RGC-32 production in Epstein-Barr virus infected white blood cells, they stop growing. This tells us that inducing the production of RGC-32 may be an important part of how Epstein-Barr virus drives white blood cells to keep growing indefinitely and become cancer cells. We have discovered news ways in which RGC-32 production is controlled in white blood cells.Our research will obtain further information on how RGC-32 production is controlled by Epstein-Barr virus and uncover how RGC-32 controls the growth of cells. This research will therefore increase our understanding of how production of RGC-32 may contribute to cancer development. In the longer term our work could open up possibilities for designing drugs to block the production or function of RGC-32 that could help in treatment of Epstein-Barr virus associated cancers and some other cancers where RGC-32 is produced at high level (e.g. breast and colon).Specifically we will determine:1. How Epstein-Barr virus drives the production of RGC-32 in white blood cells.2. How RGC-32 controls the growth of cells by affecting the different stages of the cell growth cycle. 3. How RGC-32 associates with growth control proteins and how this affects how they function.Our research will provide important information for both basic scientists and clinicians working in the field of cancer research. It could inform longer-term therapeutic strategies that may eventually benefit patients.

我们一直在研究一种人类蛋白质（RGC-32），它可能与许多癌症的发展有关。我们发现，当白细胞被癌症病毒Epstein-Barr病毒感染时，会产生RGC-32，这表明RGC-32可能与Epstein-Barr病毒相关的癌症有关。这包括许多淋巴瘤，如伯基特淋巴瘤、霍奇金淋巴瘤和移植后淋巴瘤。我们已经证明，如果我们减少eb病毒感染的白细胞中RGC-32的产生，它们就会停止生长。这告诉我们，诱导RGC-32的产生可能是爱泼斯坦-巴尔病毒驱动白细胞无限生长并成为癌细胞的重要部分。我们已经发现了在白细胞中控制RGC-32生成的新方法。我们的研究将进一步了解Epstein-Barr病毒如何控制RGC-32的产生，并揭示RGC-32如何控制细胞的生长。因此，这项研究将增加我们对RGC-32的产生如何促进癌症发展的理解。从长远来看，我们的工作可能会为设计药物来阻断RGC-32的产生或功能提供可能性，这可能有助于治疗与爱泼斯坦-巴尔病毒相关的癌症和其他一些高水平产生RGC-32的癌症（例如乳腺癌和结肠癌）。具体来说，我们将确定：1。爱泼斯坦-巴尔病毒如何驱动白细胞中RGC-32的产生。RGC-32如何通过影响细胞生长周期的不同阶段来控制细胞的生长。3. RGC-32如何与生长控制蛋白相关联，以及这如何影响它们的功能。我们的研究将为癌症研究领域的基础科学家和临床医生提供重要的信息。它可以为长期治疗策略提供信息，最终可能使患者受益。

项目成果

Increased association between Epstein-Barr virus EBNA2 from type 2 strains and the transcriptional repressor BS69 restricts EBNA2 activity

• DOI: 10.1371/journal.ppat.1007458
• 发表时间: 2019-07
• 期刊: PLoS Pathogens
• 影响因子: 6.7
• 作者: R. Ponnusamy;Ritika Khatri;Paulo B. Correia;C. Wood;E. Mancini;Paul J. Farrell;M. West

Differential proteolytic activation of the Bacillus thuringiensis Cry41Aa parasporin modulates its anticancer effect.

苏云金芽孢杆菌 Cry41Aa 副孢菌素的差异蛋白水解激活可调节其抗癌作用。

• DOI: 10.1042/bcj20190732
• 发表时间: 2019
• 期刊: The Biochemical journal
• 作者: Souissi W

Dissecting the impact of bromodomain inhibitors on the Interferon Regulatory Factor 4-MYC oncogenic axis in multiple myeloma.

• DOI: 10.1002/hon.3016
• 发表时间: 2022-08
• 期刊: HEMATOLOGICAL ONCOLOGY
• 影响因子: 3.3
• 作者: Agnarelli, Alessandro;Mitchell, Simon;Caalim, Gillian;Wood, C. David;Milton-Harris, Leanne;Chevassut, Timothy;West, Michelle J.;Mancini, Erika J.
• 通讯作者: Mancini, Erika J.

Probing the Mechanism of Action of Cry41Aa on HepG2 through the Establishment of a Resistant Subline.

• DOI: 10.3390/toxins14050319
• 发表时间: 2022-04-29
• 期刊: Toxins
• 影响因子: 4.2