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PMID: 16177824 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100.

The EMBO journal ·Vol. 24 ·No. 20 ·2005-10-19 ·Pages 3565-75

Ling PD, Peng RS, Nakajima A, Yu JH, Tan J, Moses SM, Yang WH, Zhao B, Kieff E, Bloch KD, Bloch DB

Abstract

The Epstein-Barr virus (EBV) EBNA-LP protein is important for EBV-mediated B-cell immortalization and is a potent gene-specific coactivator of the viral transcriptional activator, EBNA2. The mechanism(s) by which EBNA-LP functions as a coactivator remains an important question in the biology of EBV-induced B-cell immortalization. In this study, we found that EBNA-LP interacts with the promyelocytic leukemia nuclear body (PML NB)-associated protein Sp100 and displaces Sp100 and heterochromatin protein 1alpha (HP1alpha) from PML NBs. Interaction between EBNA-LP and Sp100 was mediated through conserved region 3 in EBNA-LP and the PML NB targeting domain in Sp100. Overexpression of Sp100 lacking the N-terminal PML NB targeting domain, but not a mutant form of Sp100 lacking the HP1alpha interaction domain, was sufficient to coactivate EBNA2 in a gene-specific manner independent of EBNA-LP. These findings suggest that Sp100 is a major mediator of EBNA-LP coactivation. These studies indicate that modulation of PML NB-associated proteins may be important for establishment of latent viral infections, and also identify a convenient model system to investigate the functions of Sp100.

MeSH Terms
Antigens, Nuclear/analysis,genetics,metabolism Autoantigens/analysis,genetics,metabolism B-Lymphocytes/virology Cell Nucleus/chemistry,metabolism Cells, Cultured Chromobox Protein Homolog 5 Chromosomal Proteins, Non-Histone/metabolism Epstein-Barr Virus Nuclear Antigens/genetics,metabolism Gene Expression Regulation, Viral Humans Nuclear Proteins/analysis,genetics,metabolism Protein Interaction Mapping Protein Structure, Tertiary Sequence Deletion Transcription, Genetic Up-Regulation/genetics Viral Proteins/analysis,metabolism
Chemicals
Antigens, Nuclear Autoantigens CBX5 protein, human Chromosomal Proteins, Non-Histone EBNA-2 protein, Human herpesvirus 4 EBNA-LP protein, Human herpesvirus 4 Epstein-Barr Virus Nuclear Antigens Nuclear Proteins Viral Proteins Chromobox Protein Homolog 5 Sp100 protein, human
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ling Paul D
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. pling@bcm.tmc.edu
Peng Rong Sheng
Nakajima Ayako
Yu Jiang H
Tan Jie
Moses Stephanie M
Yang Wei-Hong
Zhao Bo
Kieff Elliott
Bloch Kenneth D
Bloch Donald B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600820
Email
pling@bcm.tmc.edu
Published
2005-10-19
Epub
2005-00-22
Pages
3565-75
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1276704
Subset
IM
Grants
NIDDK NIH HHS · DK-051179 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7600820 PMC Full Text View journal details
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