Activation of the ERK signal transduction pathway by Epstein-Barr virus immediate-early protein Rta

• Published in: Journal of general virology Vol. 89; no. 10; pp. 2437 - 2446
• Main Authors: Lee, Yu-Hsiu, Chiu, Ya-Fang, Wang, Wen-Hung, Chang, Li-Kwan, Liu, Shih-Tung
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.10.2008; Society for General Microbiology
• Subjects: Binding, Competitive; Biological and medical sciences; Cell Line; Epstein-Barr virus; Extracellular Signal-Regulated MAP Kinases - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral; Herpesvirus 4, Human - metabolism; Humans; Immediate-Early Proteins - metabolism; Microbiology; Miscellaneous; Promoter Regions, Genetic; Protein Binding; Protein Kinases - metabolism; Signal Transduction; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription, Genetic; Transcriptional Activation; Two-Hybrid System Techniques; Ubiquitin-Protein Ligases - metabolism; Virology; Gammaherpesvirinae; Virus; Signal transduction; Microbiology; Enzyme; Herpesviridae; Transferases; Mitogen-activated protein kinase; Epstein Barr virus; Protein
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.2008/003897-0

1 Institute of Microbiology and Immunology, National Yang-Ming University, 155 Linong Street Section 2, Taipei 112, Taiwan, ROC 2 Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Taoyuan 333, Taiwan, ROC 3 Institute of Microbiology and Biochemistry, National Taiwan University, 1 Roosevelt Road Section 4, Taipei 106, Taiwan, ROC Correspondence Shih-Tung Liu cgliu{at}mail.cgu.edu.tw 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.