Bortezomib attenuates HIF-1- but not HIF-2-mediated transcriptional activation

Bortezomib attenuates HIF-1- but not HIF-2-mediated transcriptional activation

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...

1(hypoxia-inducible factor-1, HIF-1) AMPK HIF-1 AMPK AMPK HIF-1 AMPK HIF-1 HIF-1 AMPK HIF-1 AMPK

The AMP-activated protein kinase is found in all eukaryotic cells. Once activated, the kinase switches on ATP-producing catabolic pathways and switches off ATP-consuming processes,both via direct phosphorylation of downstream targets, and thus is called a cellular energy regulator . A variety of novel downstream target proteins have been discovered recently, which provide new insight into eluci...

Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1alpha C-terminal activation domain.

The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth factor (VEGF) expression as paradigmatic markers of HIF-1 activity, we found tha...

The transcription of Hypoxia-inducible factors (hif-1, hif-2) during normal development of Beluga sturgeon (Huso huso Linnaeus, 1758)

In the present study, the levels of the hypoxia-inducible factors (hif-1, hif-2) transcripts were evaluated during development of an ancient fish species, Beluga sturgeon (Huso huso) in a normal oxygen environment. The transcripts of hif-1, hif-2 were detected in all developmental time-points of H. huso from embryos to juvenile fish. Changes in normalized hif-1, hif-2 mRNA expression by using t...

Differential Regulation of the Transcriptional Activities of Hypoxia-Inducible Factor 1 Alpha (HIF-1 ) and HIF-2 in Stem Cells†