Role of the ubiquitin proteasome system in hematologic malignancies

Ubiquitination is a post-translational modification process that regulates several critical cellular processes. Ubiquitination is orchestrated by the ubiquitin proteasome system (UPS), which constitutes a cascade of enzymes that transfer ubiquitin onto protein substrates. The UPS catalyzes the destruction of many critical protein substrates involved in cancer pathogenesis. This review article focuses on components of the UPS that have been demonstrated to be deregulated by a variety of mechanisms in hematologic malignancies. These include E3 ubiquitin ligases and deubiquitinating enzymes. The prospects of specific targeting of key enzymes in this pathway that are critical to the pathogenesis of particular hematologic neoplasia are also discussed.