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Epstein-Barr virus nuclear protein EBNA3C residues critical for maintaining lymphoblastoid cell growth
- Source :
- Proceedings of the National Academy of Sciences. 106:4419-4424
- Publication Year :
- 2009
- Publisher :
- Proceedings of the National Academy of Sciences, 2009.
-
Abstract
- Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is essential for efficient conversion of primary human B lymphocytes to lymphoblastoid cell lines (LCLs) and for continued LCL growth. We used a transcomplementation assay in the context of LCLs transformed by an EBV with a conditional EBNA3C to identify the EBNA3C amino acids (aa) necessary for maintaining LCL growth. Surprisingly, we found that most EBNA3C aa were essential for continued LCL growth. Only EBNA3C mutants deleted for residues within aa 507-515, 516-620, 637-675, or 676-727 maintained full LCL growth, and EBNA3C mutants deleted for residues within aa 728-732 or 910-992 maintained slow LCL growth. In contrast, EBNA3C lacking aa 180-231, which mediate RBP-Jkappa association and are necessary for EBNA3C abrogation of EBNA2-induced transcription through RBP-Jkappa, could not support LCL growth. Furthermore, 2 EBNA3C alanine substitution mutants within aa 180-231, which were wild-type (wt) in abrogating EBNA2-mediated transcription through RBP-Jkappa, maintained LCL growth, and 2 alanine substitution mutants within aa 180-231, which were null in abrogating EBNA2-mediated transcription through RBP-Jkappa, did not maintain LCL growth. This indicates that EBNA3C regulation of transcription through RBP-Jkappa is critical to maintaining LCL growth. Several other EBNA3C functions also are critical for LCL growth, because EBNA3C mutants deleted for residues within aa 130-159, 251-506, or 733-909 were wt in abrogating transcription through RBP-Jkappa and expression level, but did not maintain LCL growth.
- Subjects :
- Herpesvirus 4, Human
Lymphoma, B-Cell
Transcription, Genetic
Mutant
Biology
medicine.disease_cause
Virus
Viral Proteins
Transcription (biology)
hemic and lymphatic diseases
otorhinolaryngologic diseases
medicine
Humans
Nuclear protein
Antigens, Viral
Alanine
Regulation of gene expression
chemistry.chemical_classification
B-Lymphocytes
Multidisciplinary
Genetic Complementation Test
Biological Sciences
Cell Transformation, Viral
Epstein–Barr virus
Virology
Molecular biology
Amino acid
stomatognathic diseases
Epstein-Barr Virus Nuclear Antigens
Gene Expression Regulation
chemistry
Immunoglobulin J Recombination Signal Sequence-Binding Protein
Mutation
Mutagenesis, Site-Directed
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 106
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....c193f37fb1261b9c5f970e4558887877