Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100.
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.
Ling
Paul D
PD
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. pling@bcm.tmc.edu
Peng
Rong Sheng
RS
Nakajima
Ayako
A
Yu
Jiang H
JH
Tan
Jie
J
Moses
Stephanie M
SM
Yang
Wei-Hong
WH
Zhao
Bo
B
Kieff
Elliott
E
Bloch
Kenneth D
KD
Bloch
Donald B
DB
D034961:Antigens, Nuclear / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001324:Autoantigens / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000821:virology*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D014764:Viral Proteins / Q000032:analysis / Q000378:metabolism*
D034961:Antigens, Nuclear; D001324:Autoantigens; C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; C402641:EBNA-2 protein, Human herpesvirus 4; C402640:EBNA-LP protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D009687:Nuclear Proteins; D014764:Viral Proteins; D000090266:Chromobox Protein Homolog 5; C066642:SP100 protein, human