Bortezomib is the first proteasomal inhibitor (PI) to be used therapeutically for treating relapse cases of multiple myeloma and mantle cell lymphoma. A proposed mechanism for its action is that it prevents the proteasomal degradation of proapoptotic proteins, leading to enhanced apoptosis. Although the α subunit of hypoxia-inducible factor (HIF)-1 is not degraded with bortezomib treatment, the...

The transcription factor hypoxia-inducible factor 1 (HIF1) facilitates the induction of enzymes necessary for anaerobic glycolysis. Luo et al. (2011) now identify pyruvate kinase (PK)-M2 as an intriguing new interacting partner for HIF1, revealing a potential mechanism for the Warburg effect, an elevation in aerobic glycolytic metabolism frequently observed in cancer.