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Basic Characteristics of Mutations
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Mutation Site
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T502N |
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Mutation Site Sentence
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Amino acids A487V, T585I, T502N, D499E, and R594K are on the exposed EBNA1 surface opposite the DNA binding interface, suggesting that they may alter potential interactions of EBNA1 with other proteins. Amino acids T524I, I528V, and L533I are buried within the protein surface and have no apparent effect on overall structure. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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EBNA-1 |
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Standardized Encoding Gene
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EBNA-1
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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28077791
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Title
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Carcinoma-risk variant of EBNA1 deregulates Epstein-Barr Virus episomal latency
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Author
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Dheekollu J,Malecka K,Wiedmer A,Delecluse HJ,Chiang AK,Altieri DC,Messick TE,Lieberman PM
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Journal
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Oncotarget
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Journal Info
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2017 Jan 31;8(5):7248-7264
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Abstract
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Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection. We identify Survivin as a host protein deficiently bound by the NPC variant of EBNA1 and show that Survivin depletion compromises EBV episome maintenance in multiple cell types. We propose that endemic variants of EBNA1 play a significant role in EBV-driven carcinogenesis by altering key regulatory interactions that destabilize latent infection.
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Sequence Data
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-
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