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Please use this identifier to cite or link to this item:
http://hdl.handle.net/123456789/784
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| Title: | A novel viral mechanism for dysregulation of β-catenin in Kaposi’s sarcoma–associated herpesvirus latency |
| Authors: | Fujimuro, Masahiro
Wu, Frederick Y.
apRhys, Colette
Kajumbula, Henry
Young, David B.
Hayward, Gary S.
Hayward, S. Diane |
| Keywords: | Viral
Kaposi's sarcoma−associated herpesvirus (KSHV)
latency-associated nuclear antigen (LANA)
Tumors |
| Issue Date: | Mar-2003 |
| Publisher: | Nature Publishing group |
| Citation: | Fujimuro, M. et al. (2003). A novel viral mechanism for dysregulation of β-catenin in Kaposi’s sarcoma–associated herpesvirus latency. Nature Medicine, 9(3): 300-306. |
| Abstract: | The Kaposi's sarcoma−associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is expressed in all KSHV-associated tumors, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We found that β-catenin is overexpressed in both PEL cells and KS tissue. Introduction of anti-LANA small interfering RNA (siRNA) into PEL cells eliminated β-catenin accumulation; LANA itself upregulated expression of β-catenin in transfected cells. LANA stabilizes β-catenin by binding to the negative regulator GSK-3β, causing a cell cycle−dependent nuclear accumulation of GSK-3β. The LANA C terminus contains sequences similar to the GSK-3β-binding domain of Axin. Disruption of this region resulted in a mutant LANA that failed to re-localize GSK-3 or stabilize β-catenin. The importance of this pathway to KSHV-driven cell proliferation was highlighted by the observation that LANA, but not mutant LANA, stimulates entry into S phase. Redistribution of GSK-3β can therefore be a source of β-catenin dysregulation in human cancers. |
| Description: | © 2003 Nature Publishing Group.
The original publication is available at http://www.nature.com/naturemedicine. |
| URI: | http://www.nature.com/naturemedicine
http://dx.doi.org/10.1038/nm829
http://hdl.handle.net/123456789/784 |
| ISSN: | 1078-8956 |
| Appears in Collections: | Research Articles (Bio-Medical)
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| kajumbula-chs-microbiology-res.pdf | | 991Kb | Adobe PDF | View/Open |
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