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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.
Young, David B.
Hayward, Gary S.
Hayward, S. Diane
Kaposi's sarcoma−associated herpesvirus (KSHV)
latency-associated nuclear antigen (LANA)
|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.|
|Appears in Collections:||Research Articles (Bio-Medical)|
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