Emerging roles of deubiquitinases in cancer-associated pathways

Abstract

Deubiquitinases (DUBs) are emerging as important regulators of many pathways germane to cancer. They may regulate the stability of key oncogenes, exemplified by USP28 stabilisation of c-Myc. Alternatively they can negatively regulate ubiquitin-dependent signalling cascades such as the NF-kappaB activation pathway. We review the current literature that associates DUBs with cancer and discuss their suitability as drug targets of the future.

Figure 1

Deubiquitinases are important regulators of oncogenes and tumour suppressors. Both overexpression and loss of function of DUBs can promote cancer. Ubiquitination of oncoproteins and tumour suppressors can promote their destabilization by targeting them for degradation (e.g., K48‐linked poly‐ubiquitination specifies proteasomal degradation), or regulate their activity (activation or inactivation). Activation here may refer to a variety of processes like translocation to the nucleus (e.g., PTEN and FOXO), or engagement in signalling protein interaction networks (TRAF6, RIP1). Specific DUBs implicated in tumourigenesis are shown with their cognate targets. Note that not all targets are shown here.