Repression by RAZ of Epstein-Barr virus bZIP transcription factor EB1 is dimerization independent.
The hallmark of Epstein-Barr virus (EBV) infection is the establishment of a viral genome transcription pattern called latency. The EBV BZLF1 gene product EB1 (also known as ZEBRA or Zta) is a transcription factor which is essential for the switch from latency to the lytic cycle. It has been proposed that latency is maintained (i) by the inhibition of EB1 translation via antisense hybridization of EBNA1 and EB1 hnRNAs, or (ii) by the inactivation of the EB1 activating function via the direct interaction of EB1 with RelA, the retinoic acid receptor and p53, or via the titration of EB1 in RAZ:EB1 inactive heterodimers that are unable to bind to DNA. RAZ, a fusion protein which contains the EB1 C-terminal dimerization and DNA-binding domains fused to the N-terminal 86 amino acids of the EBV BRLF1 gene product R, has been described as a trans-dominant negative regulator of EB1-activated transcription. We demonstrate here that although RAZ efficiently represses EB1-mediated transcriptional activation, the amount of RAZ protein expressed is incompatible with repression through the titration of EB1 in inactive EB1:RAZ heterodimers. Furthermore, we also demonstrate that RAZ efficiently represses transcription activated by an EB1 mutant carrying the GCN4 homodimerization domain (EB1 gcn4), despite the inability of RAZ and EB1 gcn4 to form stable heterodimers.
Segouffin
C
C
Unité de Virologie Humaine, ENS-INSERM, U412, Ecole Normale Superieurede Lyon, Lyon, France.
Gruffat
H
H
Sergeant
A
A
D000818:Animals; D001483:Base Sequence; D003587:Cytomegalovirus / Q000235:genetics; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins