Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate-early protein Rta.
BRCA1-associated protein 2 (BRAP2) is known to interact with the kinase suppressor of Ras 1 (KSR1), inhibiting the ERK signal transduction cascade. This study found that an Epstein-Barr virus (EBV) immediate-early protein, Rta, is a binding partner of BRAP2 in yeast and confirmed the binding in vitro by a glutathione S-transferase pull-down assay and in vivo by co-immunoprecipitation in 293(maxi-EBV) cells. Binding studies also showed that Rta and KSR1 interacted with the C-terminal 202 aa region in BRAP2. Additionally, Rta appeared to prevent the binding of KSR1 to BRAP2, activating the ERK signal transduction pathway and the transcription of an EBV immediate-early gene, BZLF1. Activation of the ERK signal transduction pathway by Rta may be critical for the maintenance of the lytic state of EBV.
Lee
Yu-Hsiu
YH
Institute of Microbiology and Immunology, National Yang-Ming University, 155 Linong Street Section 2, Taipei 112, Taiwan, ROC.
Chiu
Ya-Fang
YF
Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan 333, Taiwan, ROC.
Wang
Wen-Hung
WH
Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan 333, Taiwan, ROC.
Chang
Li-Kwan
LK
Institute of Microbiology and Biochemistry, National Taiwan University, 1 Roosevelt Road Section 4, Taipei 106, Taiwan, ROC.
Liu
Shih-Tung
ST
Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan 333, Taiwan, ROC.
D001667:Binding, Competitive; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C068382:BRLF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D017874:Immediate-Early Proteins; D015534:Trans-Activators; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D048049:Extracellular Signal-Regulated MAP Kinases