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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.

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Abbreviations

APC :

Adenomatous polyposis coli

cycD1 :

Cyclin D1

Dvl :

Dishevelled

EBV :

Epstein-Barr virus

FRAT :

Frequently rearranged in advanced T cell lymphomas

GSK-3 :

Glycogen synthase kinase-3

KS :

Kaposi’s sarcoma

KSHV :

Kaposi’s sarcoma-associated herpesvirus

LANA :

Latency-associated nuclear antigen

LEF :

Lymphoid enhancer binding factor

PEL :

Primary effusion lymphoma

Tcf :

T-cell transcription factor

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Authors and Affiliations

  1. Viral Oncology Program, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, 1650 Orleans St, Baltimore, MD 21231, USA

    Masahiro Fujimuro & S. Diane Hayward

  2. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Bunting-Blaustein Building CRB308, 1650 Orleans St, Baltimore, MD 21231, USA

    S. Diane Hayward

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  1. Masahiro Fujimuro
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Correspondence to S. Diane Hayward.

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Fujimuro, M., Hayward, S.D. Manipulation of glycogen-synthase kinase-3 activity in KSHV-associated cancers. J Mol Med 82, 223–231 (2004). https://doi.org/10.1007/s00109-003-0519-7

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  • DOI: https://doi.org/10.1007/s00109-003-0519-7

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