Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IkappaB(alpha) degradation.

ABSTRACT: The proteasome, a key component of the ubiquitin-proteasome pathway, has emerged as an important cancer therapeutic target. PS-341 (also called Bortezomib or Velcade) is the first proteasome inhibitor approved for newly diagnosed and relapsed multiple myeloma and is currently being tested in many clinical trials against other types of cancers. One proposed mechanism by which PS-341 exerts its anticancer effect is inactivation of nuclear factor-kappaB (NF-kappaB) through prevention of IkappaB(alpha) degradation. In this study, we show that PS-341 at concentrations that effectively inhibited the growth of human cancer cells, instead of increasing IkappaB(alpha) stability, paradoxically induced IkappaB(alpha) degradation. As a result, PS-341 facilitated p65 nuclear translocation and increased

SUBMITTER: Li C 

PROVIDER: S-EPMC2871478 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature