期刊
ONCOGENE
卷 27, 期 9, 页码 1189-1197出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210744
关键词
mitochondria; proteasome; BAX; BAK; BIM; NOXA
Bortezomib (Velcade, PS341) was licensed in 2003 as a first-in-class 20S proteasome inhibitor indicated for treatment of multiple myeloma, and is currently being evaluated clinically in a range of solid tumours. The mechanisms underlying its cancer cell toxicity are complex. A growing body of evidence suggests proteasome inhibition-dependent regulation of the BCL-2 family is a critical requirement. In particular, the stabilization of BH3-only proteins BIK, NOXA and BIM, appear to be essential for effecting BAX- and BAK-dependent cell death. These mechanisms are reviewed and the implications for favourable novel drug interactions are highlighted.
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