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Review
. 2011 Feb;3(2):118-131.
doi: 10.3390/v3020118. Epub 2011 Jan 28.

What has the study of the K3 and K5 viral ubiquitin E3 ligases taught us about ubiquitin-mediated receptor regulation?

Jessica M Boname  1 , Paul J Lehner  1
Affiliations
Review

What has the study of the K3 and K5 viral ubiquitin E3 ligases taught us about ubiquitin-mediated receptor regulation?

Jessica M Boname et al. Viruses. 2011 Feb.

Abstract

Cells communicate with each other and the outside world through surface receptors, which need to be tightly regulated to prevent both overstimulation and receptor desensitization. Understanding the processes involved in the homeostatic control of cell surface receptors is essential, but we are not alone in trying to regulate these receptors. Viruses, as the ultimate host pathogens, have co-evolved over millions of years and have both pirated and adapted host genes to enable viral pathogenesis. K3 and K5 (also known as MIR1 and MIR2) are viral ubiquitin E3 ligases from Kaposi's Sarcoma Associated Herpesvirus (KSHV) which decrease expression of a number of cell surface receptors and have been used to interrogate cellular processes and improve our understanding of ubiquitin-mediated receptor endocytosis and degradation. In this review, we summarize what has been learned from the study of these viral genes and emphasize their role in elucidating the complexity of ubiquitin in receptor regulation.

Keywords: E2 conjugating enzyme, ubiquitin; K3; K5; Membrane Associated RING-CH (MARCH); endocytosis; lysine11; lysine63; viral E3 ligase.

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Figures

Figure 1.
Figure 1.
Polyubiquinated MHC I lacking Lys63 linkages is poorly downregulated. (A) Flow cytometry dot plot showing HeLa K5 cells transduced with ubiquitin-GFP constructs as marked. (B) Radioimmune precipitation showing ubiquitinated class I heavy chains. Cells were pulse labeled for 10 minutes with 35S-cysteine/methionine and chased for 60 minutes with unlabeled amino acids. Cells were then lysed in 1% Triton X-100 in tris- buffered saline in the presence of protease inhibitors. Cleared lysates were subjected to immunoprecipitation with w6/32, which recognizes conformational MHC I. Following denaturation at 70 °C in 1% SDS, class I heavy chain was reprecipitated with HC10 and electrophoresed on a 9% polyacrylamide gel prior to drying and exposure to film.
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