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PMID: 7784177 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Physical and functional interaction of the Epstein-Barr virus BZLF1 transactivator with the retinoic acid receptors RAR alpha and RXR alpha.

Nucleic acids research ·Vol. 23 ·No. 10 ·1995-05-25 ·Pages 1729-36

Sista ND, Barry C, Sampson K, Pagano J

Abstract

Epstein-Barr virus (EBV) reactivation, indicated by induction of EBV early antigens from latently infected lymphoid cell lines by phorbol esters, is inhibited by retinoic acid (RA). Viral reactivation, which is triggered by the immediate-early BZLF-1 (Z) viral gene product, is repressed by retinoic acid receptors (RARs) RAR alpha and RXR alpha. These proteins negatively regulate Z-mediated transactivation of the promoter for an EBV early gene product, early antigen-diffuse (EaD). Here we confirm a direct physical interaction between the AP1-like protein Z and RXR alpha and map the domains of interaction in the Z protein and RXR alpha. The domain required for homodimerization of Z is separate from that required for its interaction with RXR alpha. Z also has the effect of repressing activation of an RAR-responsive cellular promoter (BRE). Point mutants in the dimerization domain of Z unable to interact with RXR alpha do not repress RXR alpha-mediated transactivation of BRE, the promoter for RAR beta, which suggests that interaction between the two proteins is required for this repressor effect. The domain of RXR alpha required for interaction with Z has been mapped, and is again separate from that required for homodimerization. These results indicate that a 'cross-coupling' or direct interaction between Z and RAR alpha and RXR alpha can modulate the reactivation of latent EBV infection and suggest that, reciprocally, the viral protein Z may influence cellular regulatory pathways.

MeSH Terms
Amino Acid Sequence Base Sequence Binding Sites DNA Primers DNA-Binding Proteins/chemistry,isolation & purification,metabolism Herpesvirus 4, Human/genetics,growth & development,metabolism Humans Macromolecular Substances Molecular Sequence Data Open Reading Frames Point Mutation Polymerase Chain Reaction Promoter Regions, Genetic Receptors, Retinoic Acid/chemistry,isolation & purification,metabolism Recombinant Fusion Proteins/chemistry,isolation & purification,metabolism Retinoic Acid Receptor alpha Retinoid X Receptors Sequence Deletion Trans-Activators/chemistry,isolation & purification,metabolism Transcription Factors/chemistry,isolation & purification,metabolism Transcriptional Activation Transfection Viral Proteins/metabolism Virus Activation
Chemicals
BZLF1 protein, Herpesvirus 4, Human DNA Primers DNA-Binding Proteins Macromolecular Substances RARA protein, human Receptors, Retinoic Acid Recombinant Fusion Proteins Retinoic Acid Receptor alpha Retinoid X Receptors Trans-Activators Transcription Factors Viral Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sista N D
109 UNC-Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill 27599-7295, USA.
Barry C
Sampson K
Pagano J
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/23.10.1729
Published
1995-05-25
Pages
1729-36
Language
English
Region
England
NLM ID
0411011
PMCID
PMC306929
Subset
IM
Grants
NCI NIH HHS · 2 PO1 CA19014-17A1 · United States
External Links
PubMed source DOI: 10.1093/nar/23.10.1729 PMC Full Text View journal details
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