Induction of the early growth response 1 gene by Epstein-Barr virus lytic transactivator Zta.
Early growth response 1 (Egr-1) is a cellular transcription factor involved in diverse biologic functions. Egr-1 has been associated with Epstein-Barr virus (EBV) infection, but it is still unknown whether any EBV protein regulates Egr-1 expression. In this study, we first showed that EBV reactivation is involved in upregulation of Egr-1 and that Egr-1 can be induced by Zta, an EBV lytic transactivator. Zta not only binds to the Egr-1 promoter but also activates the ERK signaling pathway to trigger binding of Elk-1 to the Egr-1 promoter. In addition, knockdown of Egr-1 significantly reduces the spontaneous expression of Zta and Rta in EBV-infected 293 cells, suggesting that a positive-feedback network involving Egr-1 is required for EBV reactivation. This study also implies that Zta has the potential to affect expression of certain genes through Egr-1.
Chang
Yao
Y
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Number 1, Section 1 Jen-Ai Road, Taipei, Taiwan.
Lee
Heng-Huan
HH
Chen
Yu-Te
YT
Lu
Jean
J
Wu
Shih-Yi
SY
Chen
Chaio-Wei
CW
Takada
Kenzo
K
Tsai
Ching-Hwa
CH
D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000502:physiology*; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000502:physiology*; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D050807:ets-Domain Protein Elk-1; D048049:Extracellular Signal-Regulated MAP Kinases