Ubiquitination is now accepted as an important process for regulating intracellular signalling and the realization that many known signalling molecules exhibit E3 ligase activity has led to great strides in our understanding of how these pathways are regulated. However, as most of the de-ubiquitinating enzymes have as yet no identified substrate, little is known about their potential role in the regulation of intracellular signalling. Here, we examine what is known about de-ubiquitinating enzymes and signalling, with particular emphasis on their role in the regulation of immune signalling and the initiation of DNA repair. In addition, we look at the evidence implicating these enzymes in the pathogenesis of diseases such as cancer and neurodegenerative diseases.

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