Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells

Mandana Mansouri, Janet Douglas, Patrick P. Rose, Kristine Gouveia, Gary Thomas, Robert E. Means, Ashlee Moses, Klaus Frueh

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The transmembrane ubiquitin ligase K5/MIR2 of Kaposi sarcoma herpesvirus (KSHV) mediates internalization and lysosomal degradation of glycoproteins involved in antigen presentation and costimulation. In endothelial cells (ECs), K5 additionally reduced expression of CD31/platelet-endothelial cell adhesion molecule (PECAM), an adhesion molecule regulating cell-cell interactions of ECs, platelets, monocytes, and T cells. K5 also reduced EC migration, a CD31-dependent process. Unlike other K5 substrates, both newly synthesized and pre-existing CD31 molecules were targeted by K5. K5 was transported to the cell surface and ubiquitinated pre-existing CD31, resulting in endocytosis and lysosomal degradation. In the endoplasmic reticulum, newly synthesized CD31 was degraded by proteasomes, which required binding of phosphofurin acidic cluster sorting protein-2 (PACS-2) to acidic residues in the carboxyterminal tail of K5. Thus, CD31, a novel target of K5, is efficiently removed from ECs by a dual degradation mechanism that is regulated by the subcellular sorting of the ubiquitin ligase. K5-mediated degradation of CD31 is likely to affect EC function in KS tumors.

Original languageEnglish (US)
Pages (from-to)1932-1940
Number of pages9
JournalBlood
Volume108
Issue number6
DOIs
StatePublished - Sep 15 2006
Externally publishedYes

Fingerprint

Kaposi's Sarcoma
Herpesviridae
Endothelial cells
Cell Adhesion Molecules
Platelets
Blood Platelets
Endothelial Cells
Degradation
Ligases
Ubiquitin
Sorting
Molecules
T-cells
Antigen Presentation
Protein Transport
Proteasome Endopeptidase Complex
Endocytosis
Cell Communication
Endoplasmic Reticulum
Cell Movement

ASJC Scopus subject areas

  • Hematology

Cite this

Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. / Mansouri, Mandana; Douglas, Janet; Rose, Patrick P.; Gouveia, Kristine; Thomas, Gary; Means, Robert E.; Moses, Ashlee; Frueh, Klaus.

In: Blood, Vol. 108, No. 6, 15.09.2006, p. 1932-1940.

Research output: Contribution to journalArticle

Mansouri M, Douglas J, Rose PP, Gouveia K, Thomas G, Means RE et al. Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood. 2006 Sep 15;108(6):1932-1940. https://doi.org/10.1182/blood-2005-11-4404
Mansouri, Mandana ; Douglas, Janet ; Rose, Patrick P. ; Gouveia, Kristine ; Thomas, Gary ; Means, Robert E. ; Moses, Ashlee ; Frueh, Klaus. / Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. In: Blood. 2006 ; Vol. 108, No. 6. pp. 1932-1940.
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