New Look of EBV LMP1 Signaling Landscape

The Epstein–Barr Virus (EBV) principal oncoprotein Latent Membrane Protein 1 (LMP1) is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily with constitutive activity. LMP1 shares many features with Pathogen Recognition Receptors (PRRs), including the use of TRAFs, adaptors, and kinase...

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Autores principales:	Ling Wang, Shunbin Ning
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	EBV LMP1 LIMD1 LUBAC p62 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/46b4200b411a4c34862978d91af4055f
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spelling	oai:doaj.org-article:46b4200b411a4c34862978d91af4055f2021-11-11T15:33:24ZNew Look of EBV LMP1 Signaling Landscape10.3390/cancers132154512072-6694https://doaj.org/article/46b4200b411a4c34862978d91af4055f2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5451https://doaj.org/toc/2072-6694The Epstein–Barr Virus (EBV) principal oncoprotein Latent Membrane Protein 1 (LMP1) is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily with constitutive activity. LMP1 shares many features with Pathogen Recognition Receptors (PRRs), including the use of TRAFs, adaptors, and kinase cascades, for signal transduction leading to the activation of NFκB, AP1, and Akt, as well as a subset of IRFs and likely the master antioxidative transcription factor NRF2, which we have gradually added to the list. In recent years, we have discovered the Linear UBiquitin Assembly Complex (LUBAC), the adaptor protein LIMD1, and the ubiquitin sensor and signaling hub p62, as novel components of LMP1 signalosome. Functionally, LMP1 is a pleiotropic factor that reprograms, balances, and perturbs a large spectrum of cellular mechanisms, including the ubiquitin machinery, metabolism, epigenetics, DNA damage response, extracellular vehicles, immune defenses, and telomere elongation, to promote oncogenic transformation, cell proliferation and survival, anchorage-independent cell growth, angiogenesis, and metastasis and invasion, as well as the development of the tumor microenvironment. We have recently shown that LMP1 induces p62-mediated selective autophagy in EBV latency, at least by contributing to the induction of p62 expression, and Reactive Oxygen Species (ROS) production. We have also been collecting evidence supporting the hypothesis that LMP1 activates the Keap1-NRF2 pathway, which serves as the key antioxidative defense mechanism. Last but not least, our preliminary data shows that LMP1 is associated with the deregulation of cGAS-STING DNA sensing pathway in EBV latency. A comprehensive understanding of the LMP1 signaling landscape is essential for identifying potential targets for the development of novel strategies towards targeted therapeutic applications.Ling WangShunbin NingMDPI AGarticleEBVLMP1LIMD1LUBACp62Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5451, p 5451 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	EBV LMP1 LIMD1 LUBAC p62 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	EBV LMP1 LIMD1 LUBAC p62 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ling Wang Shunbin Ning New Look of EBV LMP1 Signaling Landscape
description	The Epstein–Barr Virus (EBV) principal oncoprotein Latent Membrane Protein 1 (LMP1) is a member of the Tumor Necrosis Factor Receptor (TNFR) superfamily with constitutive activity. LMP1 shares many features with Pathogen Recognition Receptors (PRRs), including the use of TRAFs, adaptors, and kinase cascades, for signal transduction leading to the activation of NFκB, AP1, and Akt, as well as a subset of IRFs and likely the master antioxidative transcription factor NRF2, which we have gradually added to the list. In recent years, we have discovered the Linear UBiquitin Assembly Complex (LUBAC), the adaptor protein LIMD1, and the ubiquitin sensor and signaling hub p62, as novel components of LMP1 signalosome. Functionally, LMP1 is a pleiotropic factor that reprograms, balances, and perturbs a large spectrum of cellular mechanisms, including the ubiquitin machinery, metabolism, epigenetics, DNA damage response, extracellular vehicles, immune defenses, and telomere elongation, to promote oncogenic transformation, cell proliferation and survival, anchorage-independent cell growth, angiogenesis, and metastasis and invasion, as well as the development of the tumor microenvironment. We have recently shown that LMP1 induces p62-mediated selective autophagy in EBV latency, at least by contributing to the induction of p62 expression, and Reactive Oxygen Species (ROS) production. We have also been collecting evidence supporting the hypothesis that LMP1 activates the Keap1-NRF2 pathway, which serves as the key antioxidative defense mechanism. Last but not least, our preliminary data shows that LMP1 is associated with the deregulation of cGAS-STING DNA sensing pathway in EBV latency. A comprehensive understanding of the LMP1 signaling landscape is essential for identifying potential targets for the development of novel strategies towards targeted therapeutic applications.
format	article
author	Ling Wang Shunbin Ning
author_facet	Ling Wang Shunbin Ning
author_sort	Ling Wang
title	New Look of EBV LMP1 Signaling Landscape
title_short	New Look of EBV LMP1 Signaling Landscape
title_full	New Look of EBV LMP1 Signaling Landscape
title_fullStr	New Look of EBV LMP1 Signaling Landscape
title_full_unstemmed	New Look of EBV LMP1 Signaling Landscape
title_sort	new look of ebv lmp1 signaling landscape
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/46b4200b411a4c34862978d91af4055f
work_keys_str_mv	AT lingwang newlookofebvlmp1signalinglandscape AT shunbinning newlookofebvlmp1signalinglandscape
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New Look of EBV LMP1 Signaling Landscape

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