Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus

Mandana Mansouri, Patrick P. Rose, Ashlee Moses, Klaus Frueh

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Vascular endothelial cadherin (VE-cadherin) connects neighboring endothelial cells (ECs) via interendothelial junctions and regulates EC proliferation and adhesion during vasculogenesis and angiogenesis. The cytoplasmic domain of VE-cadherin recruits α- and β-catenins and γ-catenin, which interact with the actin cytoskeleton, thus modulating cell morphology. Dysregulation of the adherens junction/cytoskeletal axis is a hallmark of invasive tumors. We now demonstrate that the transmembrane ubiquitin ligase K5/MIR-2 of Kaposi's sarcoma-associated herpesvirus targets VE-cadherin for ubiquitin-mediated destruction, thus disturbing EC adhesion. In contrast, N-cadherin levels in K5-expressing cells were increased compared to those in control cells. Steady-state levels of α- and β-catenins and γ-catenin in K5-expressing ECs were drastically reduced due to proteasomal destruction. Moreover, the actin cytoskeleton was rearranged, resulting in the dysregulation of EC barrier function as measured by electric cell-substrate impedance sensing. Our data represent the first example of a viral protein targeting adherens junction proteins and suggest that K5 contributes to EC proliferation, vascular leakage, and the reprogramming of the EC proteome during Kaposi's sarcoma tumorigenesis.

Original languageEnglish (US)
Pages (from-to)9615-9628
Number of pages14
JournalJournal of Virology
Volume82
Issue number19
DOIs
StatePublished - Oct 2008

Fingerprint

Human herpesvirus 8
Adherens Junctions
Human Herpesvirus 8
endothelial cells
Endothelial Cells
Catenins
cadherins
blood vessels
ubiquitin
Ubiquitin
microfilaments
Actin Cytoskeleton
cell adhesion
Cell Adhesion
cell proliferation
Cell Proliferation
cells
Kaposi's Sarcoma
viral proteins
impedance

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus. / Mansouri, Mandana; Rose, Patrick P.; Moses, Ashlee; Frueh, Klaus.

In: Journal of Virology, Vol. 82, No. 19, 10.2008, p. 9615-9628.

Research output: Contribution to journalArticle

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