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Focused Review
Proteasome Inhibitor Induces Apoptosis through Induction of Endoplasmic Reticulum Stress
Andrew Fribley, and Cun-Yu Wang
volume 5 | issue 7
july 2006Pages: 745-748
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The 26S proteasome is a large multi-subunit protein complex found in the cytoplasm and nucleus of mammalian cells which plays a critical role in intracellular proteolysis. It has been found that the 26S proteasome degrades multiple important substrates which are associated with tumor growth and development. Emerging evidence demonstrates that proteasome inhibition is an innovative and effective approach for treating some human cancers. PS-341 (also known as Velcade or Bortezomib), a specific inhibitor of the 26S proteasome, has been approved for treating multiple myeloma by the FDA. PS-341 mainly exhibits its anti-cancer effect by inducing apoptosis, and has been found to affect several pro- and anti-apoptotic pathways. Activation of the transcription factor nuclear factor kappa B (NF-?B), a key survival factor, is dependent on the 26S proteasome. The inhibition of NF-κB by PS-341 has been found to induce apoptosis in several human cancer cells and is considered to be one of the primary targets of the PS-341 anti-tumor effect. More recently, studies have suggested that, in addition to the inhibition of pro-survivial NF-κB, PS-341 may induce apoptosis by stimulating pro-apoptotic endoplasmic reticulum stress through proteasome inhibition. In this review, we will mainly discuss recent progress on the elucidation of the molecular mechanism of PS-341-mediated apoptosis.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.