A novel viral mechanism for dysregulation of Β-catenin in Kaposi's sarcoma-associated herpesvirus latency

Masahiro Fujimuro, Frederick Y. Wu, Colette Aprhys, Henry Kajumbula, David B. Young, Gary Selwyn Hayward, S. Diane Hayward

Research output: Contribution to journalArticle

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-3β 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.

Original languageEnglish (US)
Pages (from-to)300-306
Number of pages7
JournalNature Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2003

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Catenins
Human Herpesvirus 8
Glycogen Synthase Kinase 3
Primary Effusion Lymphoma
Kaposi's Sarcoma
latency-associated nuclear antigen
Cell proliferation
S Phase
Small Interfering RNA
Tumors
Neoplasms
Cell Cycle
Cells
Cell Proliferation
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A novel viral mechanism for dysregulation of Β-catenin in Kaposi's sarcoma-associated herpesvirus latency. / Fujimuro, Masahiro; Wu, Frederick Y.; Aprhys, Colette; Kajumbula, Henry; Young, David B.; Hayward, Gary Selwyn; Hayward, S. Diane.

In: Nature Medicine, Vol. 9, No. 3, 01.03.2003, p. 300-306.

Research output: Contribution to journalArticle

Fujimuro, M, Wu, FY, Aprhys, C, Kajumbula, H, Young, DB, Hayward, GS & Hayward, SD 2003, 'A novel viral mechanism for dysregulation of Β-catenin in Kaposi's sarcoma-associated herpesvirus latency', Nature Medicine, vol. 9, no. 3, pp. 300-306. https://doi.org/10.1038/nm829
Fujimuro, Masahiro ; Wu, Frederick Y. ; Aprhys, Colette ; Kajumbula, Henry ; Young, David B. ; Hayward, Gary Selwyn ; Hayward, S. Diane. / A novel viral mechanism for dysregulation of Β-catenin in Kaposi's sarcoma-associated herpesvirus latency. In: Nature Medicine. 2003 ; Vol. 9, No. 3. pp. 300-306.
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