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

The Kaposi'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 beta-catenin is overexpressed in two KSHV-associated cancers, Kaposi's sarcoma and primary effusion lymphoma. Investigation of the underlying defect in beta-catenin regulation revealed that the KSHV-encoded LANA protein stabilizes beta-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 beta-catenin can be dysregulated and contribute to human cancer.