Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator

D. Marshall, Clare Sample

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA- 3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA- binding protein RBP-Jκ. In addition, direct interaction between RBP-Jκ and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-Jκ sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.

Original languageEnglish (US)
Pages (from-to)3624-3630
Number of pages7
JournalJournal of Virology
Volume69
Issue number6
StatePublished - 1995

Fingerprint

nuclear antigens
Epstein-Barr Virus Nuclear Antigens
Human herpesvirus 4
transcription factors
transcriptional activation
Transcriptional Activation
DNA-Binding Proteins
Response Elements
Viral Proteins
DNA-binding proteins
DNA-binding domains
Nuclear Proteins
epstein-barr virus EBNA-3C
Glutamine
Human Herpesvirus 4
response elements
Reporter Genes
viral proteins
nuclear proteins
transfection

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

@article{b3be77cb355e4832b98e41dac258af52,
title = "Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator",
abstract = "Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA- 3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA- binding protein RBP-Jκ. In addition, direct interaction between RBP-Jκ and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-Jκ sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.",
author = "D. Marshall and Clare Sample",
year = "1995",
language = "English (US)",
volume = "69",
pages = "3624--3630",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator. / Marshall, D.; Sample, Clare.

In: Journal of Virology, Vol. 69, No. 6, 1995, p. 3624-3630.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator

AU - Marshall, D.

AU - Sample, Clare

PY - 1995

Y1 - 1995

N2 - Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA- 3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA- binding protein RBP-Jκ. In addition, direct interaction between RBP-Jκ and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-Jκ sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.

AB - Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is one of five viral nuclear proteins that are essential for EBV-induced immortalization of primary human B lymphocytes in vitro. Previous studies have implied that EBNA-3C acts as a transcription factor. Using transient transfection assays, we demonstrate that EBNA-3C has two effects on reporter genes that are linked to the latent membrane protein 1 promoter, (i) low-level activation by EBNA- 3C alone, as well as potentiation of EBNA-2-mediated transactivation, and (ii) inhibition of the normally strong activation mediated by EBNA-2. These two disparate effects seem to be mediated at different stages following cell feeding. The inhibitory effect of EBNA-3C was localized to a known EBNA-2 response element that had previously been shown to be recognized by the DNA- binding protein RBP-Jκ. In addition, direct interaction between RBP-Jκ and EBNA-3C was observed by coimmunoprecipitation. Activation by EBNA-3C, however, seems to be achieved via sequences that are distinct from RBP-Jκ sites, since activation remained even after these sites had been mutated. Consistent with its ability to activate transcription, a region of EBNA-3C which has homology to the glutamine-rich activation domain of Sp1 can function as a transcription activation domain when it is fused to the heterologous DNA-binding domain of Gal4 and can partially restore the activity of a mutant EBNA-2 protein with a deletion in the transactivation domain. Collectively, these data strongly support the role of EBNA-3C as a transcriptional regulator.

UR - http://www.scopus.com/inward/record.url?scp=0029013590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029013590&partnerID=8YFLogxK

M3 - Article

VL - 69

SP - 3624

EP - 3630

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -