國家衛生研究院 NHRI:Item 3990099045/3593
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    题名: The Epstein-Barr virus replication and transcription activator, Rta/BRLF1, induces cellular senescence in epithelial cells
    作者: Chen, YL;Chen, YJ;Tsai, WH;Ko, YC;Chen, JY;Lin, SF
    贡献者: National Institute of Cancer Research
    摘要: Epstein-Barr Virus (EBV) replication and transcription activator (Rta/BRLF1) is an immediate-early transcription factor that controls the conversion of the latent viral genome into one undergoing lytic replication. By using a doxycycline-inducible expression system, the present study demonstrates that EBV Rta efficiently elicits growth arrest in the human epithelial cell line HEK293. In cells arrested by EBV Rta, the expression of p21 (CDKN1A), p27 (CDKN1B) and cyclin E were increased. In contrast, the levels of cyclin D1, CDK4 and CDK6 were sharply decreased. Activation of the host cell DNA damage response (DDR), indicated by the increasing phosphorylation of H2AX and p53 Ser15, was observed on day 3 and day 5 after EBV Rta expression, respectively. Finally, EBV Rta arrested cells exhibited strong senescence-associated β-galactosidase staining on day 10 after doxycycline induction. Together, these results indicate that, in addition to triggering viral lytic replication in epithelial cells, EBV Rta concurrently initiates a cellular senescence program that was previously undocumented. This finding, showing Rta may be centrally involved in inducing a host cell state amenable to efficient viral reproduction, in addition to its previously characterized regulation of viral transcription, provides new perspectives in understanding EBV pathogenesis. ?2009 Landes Bioscience.
    日期: 2009-01-01
    關聯: Cell Cycle. 2009 Jan 1;8(1):58-65.
    Link to: http://www.landesbioscience.com/journals/cc/article/7411/
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1538-4101&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000262137700015
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=60749137075
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