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Vaccinia virus virulence factor N1 can be ubiquitylated on multiple lysine residues.

Maluquer de Motes, C, Schiffner, T, Sumner, RP and Smith, GL (2014) Vaccinia virus virulence factor N1 can be ubiquitylated on multiple lysine residues. J Gen Virol, 95 (Pt 9). pp. 2038-2049.

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Abstract

Ubiquitylation is a covalent post-translational modification that regulates protein stability and is involved in many biological functions. Proteins may be modified with mono-ubiquitin or ubiquitin chains. Viruses have evolved multiple mechanisms to perturb the cell ubiquitin system and manipulate it to their own benefit. Here, we report ubiquitylation of vaccinia virus (VACV) protein N1. N1 is an inhibitor of the nuclear factor NF-κB and apoptosis that contributes to virulence, has a Bcl-2-like fold, and is highly conserved amongst orthopoxviruses. The interaction between N1 and ubiquitin occurs at endogenous protein levels during VACV infection and following ectopic expression of N1. Biochemical analysis demonstrated that N1 is covalently ubiquitylated, and heterodimers of ubiquitylated and non-ubiquitylated N1 monomers were identified, suggesting that ubiquitylation does not inhibit N1 dimerization. Studies with other VACV Bcl-2 proteins, such as C6 or B14, revealed that although these proteins also interact with ubiquitin, these interactions are non-covalent. Finally, mutagenesis of N1 showed that ubiquitylation occurs in a conventional lysine-dependent manner at multiple acceptor sites because only an N1 allele devoid of lysine residues remained unmodified. Taken together, we described a previously uncharacterized modification of the VACV protein N1 that provided a new layer of complexity to the biology of this virulence factor, and provided another example of the intricate interplay between poxviruses and the host ubiquitin system.

Item Type: Article
Authors :
NameEmailORCID
Maluquer de Motes, Cc.maluquerdemotes@surrey.ac.ukUNSPECIFIED
Schiffner, TUNSPECIFIEDUNSPECIFIED
Sumner, RPUNSPECIFIEDUNSPECIFIED
Smith, GLUNSPECIFIEDUNSPECIFIED
Date : September 2014
Identification Number : https://doi.org/10.1099/vir.0.065664-0
Uncontrolled Keywords : Animals, Apoptosis, Cell Line, Cercopithecus aethiops, Dimerization, HEK293 Cells, Humans, Lysine, Macrophages, Mice, Mutation, NF-kappa B, Ubiquitination, Vaccinia, Vaccinia virus, Viral Proteins, Virulence Factors
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:15
Last Modified : 17 May 2017 14:48
URI: http://epubs.surrey.ac.uk/id/eprint/827044

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