ArticleJournal of virology2010
Cellular corepressor TLE2 inhibits replication-and-transcription- activator-mediated transactivation and lytic reactivation of Kaposi's sarcoma-associated herpesvirus.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Review
- RETRACTED: Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.PLoS pathogens · 2021Article
- The prognostic role of the Transducin-like Enhancer of split protein family in lung adenocarcinoma.Translational lung cancer research · 2021Article
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- TLE2 is associated with favorable prognosis and regulates cell growth and gemcitabine sensitivity in pancreatic cancer.Annals of translational medicine · 2020Article
- Article
- NCOA2 promotes lytic reactivation of Kaposi's sarcoma-associated herpesvirus by enhancing the expression of the master switch protein RTA.PLoS pathogens · 2019Article
- Antiviral activity of a purine synthesis enzyme reveals a key role of deamidation in regulating protein nuclear import.Science advances · 2019Article
- Polyglutamine Repeats in Viruses.Molecular neurobiology · 2019Review
- Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.Journal of virology · 2019Article
- ARID3B: a Novel Regulator of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle.Journal of virology · 2016Article
- Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway.PLoS pathogens · 2016Article
- TLE3 represses colorectal cancer proliferation by inhibiting MAPK and AKT signaling pathways.Journal of experimental & clinical cancer research : CR · 2016Article
- NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway.Cancer biology & therapy · 2016Article
- Kaposi's sarcoma-associated herpesvirus microRNAs repress breakpoint cluster region protein expression, enhance Rac1 activity, and increase in vitro angiogenesis.Journal of virology · 2015Article
- KSHV reactivation and novel implications of protein isomerization on lytic switch control.Viruses · 2015Review
- Carboxyl-terminal amino acids 1052 to 1082 of the latency-associated nuclear antigen (LANA) interact with RBP-Jκ and are responsible for LANA-mediated RTA repression.Journal of virology · 2012Article
- Suppressive regulation of KSHV RTA with O-GlcNAcylation.Journal of biomedical science · 2012Article
- KSHV Rta Promoter Specification and Viral Reactivation.Frontiers in microbiology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replication and transcription activator (RTA) encoded by open reading frame 50 (ORF50) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential and sufficient to initiate lytic reactivation. RTA activates its target genes through direct binding with high affinity to its responsive elements or by interaction with cellular factors, such as RBP-Jkappa, Ap-1, C/EBP-alpha, and Oct-1. In this study, we identified transducin-like enhancer of split 2 (TLE2) as a novel RTA binding protein by using yeast two-hybrid screening of a human spleen cDNA library. The interaction between TLE2 and RTA was confirmed by glutathione S-transferase (GST) binding and coimmunoprecipitation assays. Immunofluorescence analysis showed that TLE2 and RTA were colocalized in the same nuclear compartment in KSHV-infected cells. This interaction recruited TLE2 to RTA bound to its recognition sites on DNA and repressed RTA auto-activation and transactivation activity. Moreover, TLE2 also inhibited the induction of lytic replication and virion production driven by RTA. We further showed that the Q (Gln-rich), SP (Ser-Pro-rich), and WDR (Trp-Asp repeat) domains of TLE2 and the Pro-rich domain of RTA were essential for this interaction. RBP-Jkappa has been shown previously to bind to the same Pro-rich domain of RTA, and this binding can be subject to competition by TLE2. In addition, TLE2 can form a complex with RTA to access the cognate DNA sequence of the RTA-responsive element at different promoters. Intriguingly, the transcription level of TLE2 could be upregulated by RTA during the lytic reactivation process. In conclusion, we identified a new RTA binding protein, TLE2, and demonstrated that TLE2 inhibited replication and transactivation mediated by RTA. This provides another potentially important mechanism for maintenance of KSHV viral latency through interaction with a host protein.
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