PMID- 8618882
OWN - NLM
STAT- MEDLINE
DCOM- 19960607
LR  - 20191210
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 92
IP  - 26
DP  - 1995 Dec 19
TI  - Functional antagonism between the retinoic acid receptor and the viral 
      transactivator BZLF1 is mediated by protein-protein interactions.
PG  - 12265-9
AB  - The Epstein-Barr virus-encoded protein BZLF1 is a member of the basic leucine 
      zipper (bZip) family of transcription factors. Like several other members of the 
      bZip family, transcriptional activity of BZLF1 is modulated by retinoic acid 
      receptors (RARs). We present evidence that the RAR alpha and BZLF1 can 
      reciprocally repress each other's transcriptional activation by a newly 
      discovered mechanism. Analysis of RAR alpha mutants in transfection studies 
      reveals that the DNA binding domain is sufficient for inhibition of BZLF1 
      activity. Analysis of BZLF1 mutants indicates that both the coiled-coil 
      dimerization domain and a region containing the transcriptional activation domain 
      of BZLF1 are required for transrepression. Coimmunoprecipitation experiments 
      demonstrate physical interactions between RAR alpha and BZLF1 in vivo. 
      Furthermore, glutathione S-transferase-pulldown assays reveal that these 
      protein-protein interactions are mediated by the coiled-coil dimerization domain 
      of BZLF1 and the DNA binding domain of RAR alpha. While RAR alpha is unable to 
      recognize BZLF1 binding sites, the RAR alpha can be tethered to the DNA by 
      forming a heteromeric complex with BZLF1 bound to DNA. Tethering RARs via 
      protein-protein interactions onto promoter DNA suggest a mechanism through which 
      RARs might gain additional levels of transcriptional regulation.
FAU - Pfitzner, E
AU  - Pfitzner E
AD  - Institut fur Experimentelle Krebsforschung, Klinik fur Tumorbiologie, Universitat 
      Freiburg, Germany.
FAU - Becker, P
AU  - Becker P
FAU - Rolke, A
AU  - Rolke A
FAU - Schule, R
AU  - Schule R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RARA protein, human)
RN  - 0 (Rara protein, mouse)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Proteins)
RN  - EC 2.5.1.18 (Glutathione Transferase)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - DNA-Binding Proteins/biosynthesis/isolation & purification/*metabolism
MH  - Glutathione Transferase/biosynthesis
MH  - Herpesvirus 4, Human/genetics/metabolism
MH  - Immunoblotting
MH  - Mice
MH  - Molecular Sequence Data
MH  - Receptors, Retinoic Acid/biosynthesis/isolation & purification/*metabolism
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Recombinant Proteins/biosynthesis/isolation & purification/metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Trans-Activators/biosynthesis/isolation & purification/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Viral Proteins/metabolism
PMC - PMC40337
EDAT- 1995/12/19 00:00
MHDA- 1995/12/19 00:01
PMCR- 1996/06/19
CRDT- 1995/12/19 00:00
PHST- 1995/12/19 00:00 [pubmed]
PHST- 1995/12/19 00:01 [medline]
PHST- 1995/12/19 00:00 [entrez]
PHST- 1996/06/19 00:00 [pmc-release]
AID - 10.1073/pnas.92.26.12265 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12265-9. doi: 
      10.1073/pnas.92.26.12265.