Awasthi Prankur, Dwivedi Manish, Kumar Dhruv, Hasan Saba
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India.
School of Health Sciences and Technology, UPES University Dehradun, Uttarakhand, India.
Life Sci. 2023 Jan 15;313:121261. doi: 10.1016/j.lfs.2022.121261. Epub 2022 Dec 7.
Numerous lymphomas, carcinomas, and other disorders have been associated with Epstein-Barr Virus (EBV) infection. EBV's carcinogenic potential can be correlated to latent membrane protein 1 (LMP1), which is essential for fibroblast and primary lymphocyte transformation. LMP1, a transmembrane protein with constitutive activity, belongs to the tumour necrosis factor receptor (TNFR) superfamily. LMP1 performs number of role in the life cycle of EBV and the pathogenesis by interfering with, reprogramming, and influencing a vast range of host cellular activities and functions that are getting well-known but still poorly understood. LMP1, pleiotropically perturbs, reprograms and balances a wide range of various processes of cell such as extracellular vesicles, epigenetics, ubiquitin machinery, metabolism, cell proliferation and survival, and also promotes oncogenic transformation, angiogenesis, anchorage-independent cell growth, metastasis and invasion, tumour microenvironment. By the help of various experiments, it is proven that EBV-encoded LMP1 activates multiple cell signalling pathways which affect antigen presentation, cell-cell interactions, chemokine and cytokine production. Therefore, it is assumed that LMP1 may perform majorly in EBV associated malignancies. For the development of novel techniques toward targeted therapeutic applications, it is essential to have a complete understanding of the LMP1 signalling landscape in order to identify potential targets. The focus of this review is on LMP1-interacting proteins and related signalling processes. We further discuss tactics for using the LMP1 protein as a potential therapeutic for cancers caused by the EBV.
许多淋巴瘤、癌和其他病症都与爱泼斯坦-巴尔病毒(EBV)感染有关。EBV的致癌潜力可与潜伏膜蛋白1(LMP1)相关联,LMP1对成纤维细胞和原代淋巴细胞转化至关重要。LMP1是一种具有组成型活性的跨膜蛋白,属于肿瘤坏死因子受体(TNFR)超家族。LMP1在EBV的生命周期和发病机制中发挥多种作用,它通过干扰、重新编程和影响大量宿主细胞活动和功能来实现,这些活动和功能虽已广为人知,但仍了解不足。LMP1多效性地扰乱、重新编程并平衡细胞的多种不同过程,如细胞外囊泡、表观遗传学、泛素机制、代谢、细胞增殖和存活,还促进致癌转化、血管生成、不依赖贴壁的细胞生长、转移和侵袭以及肿瘤微环境。通过各种实验证明,EBV编码的LMP1激活多种细胞信号通路,这些通路影响抗原呈递、细胞间相互作用、趋化因子和细胞因子的产生。因此,推测LMP1可能在EBV相关恶性肿瘤中起主要作用。为了开发针对靶向治疗应用的新技术,全面了解LMP1信号通路景观以识别潜在靶点至关重要。本综述的重点是LMP1相互作用蛋白和相关信号过程。我们还将进一步讨论将LMP1蛋白用作EBV所致癌症潜在治疗方法的策略。