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Mediators of Inflammation
Volume 2016 (2016), Article ID 3481371, 13 pages
http://dx.doi.org/10.1155/2016/3481371
Review Article

Deubiquitinases: Novel Therapeutic Targets in Immune Surveillance?

1Manchester Collaborative Centre for Inflammation Research, University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK
2Department of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, 1355 Museum Drive, Gainesville, FL 32611-0700, USA

Received 24 March 2016; Revised 1 June 2016; Accepted 4 July 2016

Academic Editor: Luca Cantarini

Copyright © 2016 Gloria Lopez-Castejon and Mariola J. Edelmann. 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

Inflammation is a protective response of the organism to tissue injury or infection. It occurs when the immune system recognizes Pathogen-Associated Molecular Patterns (PAMPs) or Damage-Associated Molecular Pattern (DAMPs) through the activation of Pattern Recognition Receptors. This initiates a variety of signalling events that conclude in the upregulation of proinflammatory molecules, which initiate an appropriate immune response. This response is tightly regulated since any aberrant activation of immune responses would have severe pathological consequences such as sepsis or chronic inflammatory and autoimmune diseases. Accumulative evidence shows that the ubiquitin system, and in particular ubiquitin-specific isopeptidases also known as deubiquitinases (DUBs), plays crucial roles in the control of these immune pathways. In this review we will give an up-to-date overview on the role of DUBs in the NF-κB pathway and inflammasome activation, two intrinsically related events triggered by activation of the membrane TLRs as well as the cytosolic NOD and NLR receptors. Modulation of DUB activity by small molecules has been proposed as a way to control dysregulation or overactivation of these key players of the inflammatory response. We will also discuss the advances and challenges of a potential use of DUBs as therapeutic targets in inflammatory pathologies.