Journal of Molecular Medicine

, Volume 82, Issue 4, pp 223–231

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

Authors

  • Masahiro Fujimuro
    • Viral Oncology Program, Sidney Kimmel Cancer CenterJohns Hopkins School of Medicine
    • Viral Oncology Program, Sidney Kimmel Cancer CenterJohns Hopkins School of Medicine
    • The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins School of Medicine
Review

DOI: 10.1007/s00109-003-0519-7

Cite this article as:
Fujimuro, M. & Hayward, S.D. J Mol Med (2004) 82: 223. doi:10.1007/s00109-003-0519-7

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.

Keywords

Kaposi’s sarcoma-associated herpesvirus Latency-associated nuclear antigen GSK-3 β-Catenin Wnt pathway

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

Copyright information

© Springer-Verlag 2004