Table of Contents
ISRN Virology
Volume 2014 (2014), Article ID 989160, 14 pages
http://dx.doi.org/10.1155/2014/989160
Research Article

The Mre11 Cellular Protein Is Modified by Conjugation of Both SUMO-1 and SUMO-2/3 during Adenovirus Infection

1Facultad de Ciencias, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, 62209 Cuernavaca, MOR, Mexico
2Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany
3European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany

Received 18 January 2014; Accepted 9 March 2014; Published 7 April 2014

Academic Editors: M. Magnani and D. A. Ornelles

Copyright © 2014 Elizabeth Castillo-Villanueva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The adenovirus type 5 (Ad5) E1B 55 kDa and E4 Orf6 proteins assemble a Cullin 5-E3 ubiquitin (Ub) ligase that targets, among other cellular proteins, p53 and the Mre11-Rad50-Nbs1 (MRN) complex for degradation. The latter is also inhibited by the E4 Orf3 protein, which promotes the recruitment of Mre11 into specific nuclear sites to promote viral DNA replication. The activities associated with the E1B 55 kDa and E4 Orf6 viral proteins depend mostly on the assembly of this E3-Ub ligase. However, E1B 55 kDa can also function as an E3-SUMO ligase, suggesting not only that regulation of cellular proteins by these viral early proteins may depend on polyubiquitination and proteasomal degradation but also that SUMOylation of target proteins may play a key role in their activities. Since Mre11 is a target of both the E1B/E4 Orf6 complex and E4 Orf3, we decided to determine whether Mre11 displayed similar properties to those of other cellular targets, in Ad5-infected cells. We have found that during Ad5-infection, Mre11 is modified by SUMO-1 and SUMO-2/3 conjugation. Unexpectedly, SUMOylation of Mre11 is not exclusively dependent on E1B 55 kDa, E4 Orf6, or E4 Orf3, rather it seems to be influenced by a molecular interplay that involves each of these viral early proteins.