Deubiquitinating Enzymes

The modification of proteins through the addition and removal of ubiquitin molecules is a fundamental cellular function.1,2 Proteasomal degradation, localization, and conformation can all be regulated through the addition of ubiquitin molecules by ubiquitin ligases as well as their removal by deubiquitinases (DUBs).1-4 Given the essential role of these processes in cellular growth and proliferation, it is not surprising that dysregulation of the ubiquitin pathway is implicated in tumorigenesis.1-3

Several DUB enzymes have been identified as tumor suppressors and oncogenes in non-Hodgkin lymphoma (NHL), including cases of diffuse large B-cell lymphoma, Burkitt lymphoma, and T-cell lymphoma.1,2 Preclinical studies show that targeting of DUB enzymes with small-molecule inhibitors reduces the survival and proliferation of malignant cells,3 suggesting that they may be potential therapeutic targets for malignancies, including NHL.1-3

AMP, adenosine monophosphate; ATP adenosine triphosphate; DUB, deubiquitinase; ub, ubiquitin.


  1. Shi D, et al. Cancer Biol Ther. 2010;10:737-747. PMID: 20930542
  2. Hussain S, et al. Cell Cycle. 2009;8:1688-1697. PMID: 19448430
  3. Fraile JM, et al. Oncogene. 2012;31:2373-2388. PMID: 21996736
  4. Crawford LJ, et al. Blood Rev. 2013;27:297-304. PMID: 24183816