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The ubiquitin-proteasome system: A novel target for anticancer and anti-inflammatory drug research


The ubiquitin-proteasome system is responsible for the degradation of most intracellular proteins, including those that control cell cycle progression, apoptosis, signal transduction and the NF-κB transcriptional pathway. Aberrations in the ubiquitin-proteasome system underlie the pathogenesis of many human diseases, so both the ubiquitin-conjugating system and the 20S proteasome are important targets for drug discovery. This article presents a few of the most important examples of the small molecule inhibitors and modulators targeting the ubiquitin-proteasome system, their mode of action, and their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases.



acute myeloid leukemia


acute renal failure


bone marrow stromal cells


β-transducin repeat containing protein


cyclindependent kinase






chronic lymphocytic leukemia






deubiquitinating enzyme


ubiquitin-activating enzyme


ubiquitin-conjugating enzyme


ubiquitin-protein ligase




human counterpart of Mdm2


hypoxia inducible factor


IκB kinase




interferon gamma


low-molecular-mass polypeptide


murine double minute 2


metionine aminopeptidase-2


major histocompatibility complex


multiple myeloma


nuclear factor-kappaB


phosphorylated inhibitor-κβ


proteolytic targeting chimeric molecules


phosphorylated von Hippel-Lindau tumor suppressor


reactivation of p53 and induction of tumor cell apoptosis


complex formed by Skp1, cullin and F-box protein


small interfering RNA


S-phase kinase associated protein 2


small molecule proteolysis inducers




tumor necrosis factor


ubiquitin-proteasome system


various leukocyte adhesion molecules


vascular endothelial growth factor


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Correspondence to Halina Ostrowska.

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Paper authored by participants of the international conference: XXXIV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, Zakopane, March 7–11, 2007, “The Cell and Its Environment”. Publication cost was partially covered by the organisers of this meeting.

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Ostrowska, H. The ubiquitin-proteasome system: A novel target for anticancer and anti-inflammatory drug research. Cell Mol Biol Lett 13, 353–365 (2008).

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  • E3 ubiquitin ligases
  • Proteasome
  • Inhibitors
  • Modulators
  • Therapeutic potential
  • Cancer
  • Stroke
  • Cardiovascular diseases