Proteasome Inhibitors

Proteasome inhibitors suppress the function of the proteasome, which results in apoptosis

The proteasome is a highly conserved and ubiquitously expressed multicatalytic proteinase complex. It is essential for normal cell function and survival because of its critical role in intracellular protein degradation. The proteasome has been described as the cell’s garbage disposal system, as it degrades proteins that are tagged for destruction. The proteasome also plays a part in cell cycle regulation, gene transcription, and apoptosis by controlling expression levels of proteins involved in these pathways.1

Due to its function in regulating these pathways, numerous studies have shown that the proteasome is particularly important in malignant cell survival and proliferation; cancer cells are more susceptible to proteasome inhibition than normal cells.1‑6 The downstream effects of proteasome inhibitor anticancer activity appear to vary depending on the tumor model tested.1 However, it is clear that many pathways can be affected. Some of the key proteins regulated by the proteasome include nuclear factor kB (NFkB; IkB), p53, p21, p27, Bax and p44/42.1

  1. Voorhees PM, et al. Clin Cancer Res. 2003;9:6316-6325.
  2. Orlowski RZ, et al. Cancer Res. 1998;58:4342-4348.
  3. Masdehors P, et al. Br J Haematol. 1999;105:752-757.
  4. Soligo D, et al. Br J Haematol. 2001;113:126-135.
  5. Hideshima T, et al. Cancer Res. 2001;61:3071-3076.
  6. Guzman M. L, et al. Proc Natl Acad Sci U S A. 2002;99:16220-16225.