Advertisement

 

 

Characterization of E3 ligases involved in lysosomal sorting of the HIV-1 restriction factor BST2.

Characterization of E3 ligases involved in lysosomal sorting of the HIV-1 restriction factor BST2.
Author Information (click to view)

Roy N, Pacini G, Berlioz-Torrent C, Janvier K,


Roy N, Pacini G, Berlioz-Torrent C, Janvier K, (click to view)

Roy N, Pacini G, Berlioz-Torrent C, Janvier K,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Journal of cell science 2017 03 20() pii 10.1242/jcs.195412

Abstract

The cellular protein BST2/ Tetherin acts as a major intrinsic antiviral protein that prevents the release of enveloped viruses by trapping nascent viral particles at the surface of infected cells. Viruses have evolved specific strategies to displace BST2 from viral budding sites in order to promote virus egress. In HIV-1, the accessory protein Vpu counters BST2 antiviral activity and promotes sorting of BST2 for lysosomal degradation. Vpu increases poly-ubiquitination of BST2 through recruitment of the E3 ligase complex SCF adaptor β-TrCP, a post translation modification required for Vpu-induced BST2 down-regulation. Herein, we further investigated the role of the ubiquitination machinery in the lysosomal sorting of BST2. Using a small siRNA screen we highlighted two additional regulators of BST2 constitutive ubiquitination and sorting to the lysosomes: the E3 ubiquitin ligases NEDD4 and MARCH8. Interestingly, Vpu does not hijack the cellular machinery constitutively involved in BST2 ubiquitination to sort BST2 for degradation in the lysosomes, but instead promotes the recognition of BST2 by β-TrCP. Altogether, our results provide further understanding of the mechanisms underlying BST2 turnover in cells.

Submit a Comment

Your email address will not be published. Required fields are marked *

8 + 19 =

[ HIDE/SHOW ]