, Volume 82, Issue 4, pp 223-231
Date: 09 Jan 2004

Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers

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Abstract

The Kapsosi’s sarcoma-associated herpesvirus, KSHV, is associated with cancers that have increased incidence in patients who are also HIV positive or who have undergone organ transplantation. It has recently been observed that β-catenin is overexpressed in two KSHV-associated cancers, Kaposi’s sarcoma and primary effusion lymphoma. Investigation of the underlying defect in β-catenin regulation revealed that the KSHV-encoded LANA protein stabilizes β-catenin by binding to the negative regulator GSK-3, causing a cell-cycle-dependent nuclear accumulation of GSK-3. Thus, redistribution of GSK-3 has been identified as yet another mechanism through which β-catenin can be dysregulated and contribute to human cancer.