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- W2071580019 abstract "Cellular protein degradation pathways can be utilized by viruses to establish an environment that favors their propagation. Here we report that the Kaposi's sarcoma–associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) directly functions as a component of the EC5S ubiquitin complex targeting the tumor suppressors von Hippel-Lindau (VHL) and p53 for degradation. We have characterized a suppressor of cytokine signaling box-like motif within LANA composed of an Elongin B and C box and a Cullin box, which is spatially located at its amino and carboxyl termini. This motif is necessary for LANA interaction with the Cul5–Elongin BC complex, to promote polyubiquitylation of cellular substrates VHL and p53 in vitro via its amino- and carboxyl-terminal binding domain, respectively. In transfected cells as well as KSHV-infected B lymphoma cells, LANA expression stimulates degradation of VHL and p53. Additionally, specific RNA interference–mediated LANA knockdown stabilized VHL and p53 in primary effusion lymphoma cells. Thus, manipulation of tumor suppressors by LANA potentially provides a favorable environment for progression of KSHV-infected tumor cells." @default.
- W2071580019 created "2016-06-24" @default.
- W2071580019 creator A5021454757 @default.
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- W2071580019 creator A5040642105 @default.
- W2071580019 creator A5071309906 @default.
- W2071580019 creator A5085330501 @default.
- W2071580019 date "2006-10-27" @default.
- W2071580019 modified "2023-10-14" @default.
- W2071580019 title "EC5S Ubiquitin Complex Is Recruited by KSHV Latent Antigen LANA for Degradation of the VHL and p53 Tumor Suppressors" @default.
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- W2071580019 doi "https://doi.org/10.1371/journal.ppat.0020116" @default.
- W2071580019 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1626105" @default.
- W2071580019 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17069461" @default.
- W2071580019 hasPublicationYear "2006" @default.
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