NAD(P)H Oxidases Regulate HIF-2α Protein Expression*

@article{Block2007NADPHOR,
  title={NAD(P)H Oxidases Regulate HIF-2$\alpha$ Protein Expression*},
  author={K. Block and Y. Gorin and P. Hoover and P. Williams and Tomasz Chelmicki and R. Clark and T. Yoneda and H. Abboud},
  journal={Journal of Biological Chemistry},
  year={2007},
  volume={282},
  pages={8019 - 8026}
}
Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is linked to the development of hereditary and sporadic renal cell carcinoma (RCC). In the absence of VHL, the α subunits of heterodimeric hypoxia-inducible transcription factors (HIF-1α and HIF-2α) are stabilized. Reactive oxygen species, generated by NAD(P)H oxidases, are involved in signaling cascades of malignant growth. We show that in VHL-deficient cells p22phox, Nox4 protein levels and NADPH-dependent superoxide… Expand

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References

SHOWING 1-10 OF 31 REFERENCES
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
TLDR
It is indicated that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF α-subunits, which may underlie the angiogenic phenotype of VHL-associated tumours. Expand
Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL-/- tumors.
TLDR
The data suggest that deregulation of hypoxia-inducible genes in VHL-/- cells can be attributed mainly to deregulation of HIF and validate HIF as a therapeutic anticancer drug target. Expand
PI3K/Akt Is Required for Heat Shock Proteins to Protect Hypoxia-inducible Factor 1α from pVHL-independent Degradation*
TLDR
It is concluded that PI3K/Akt contributes to HIF-1α stabilization by provoking expression of heat shock proteins. Expand
NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells.
TLDR
Results indicate that ROS generated by the newly described NOX5 oxidase are essential for prostate cancer growth, possibly by providing trophic intracellular oxidant tone that retards programmed cell death. Expand
Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species.
TLDR
It is concluded that hypoxic upregulation of Nox1 and subsequently augmented ROS generation may activate HIF-1-dependent pathways. Expand
Reactive Oxygen Species Produced by NAD(P)H Oxidase Inhibit Apoptosis in Pancreatic Cancer Cells*
TLDR
The results show that growth factor-induced ROS produced by NAD(P)H oxidase (probably Nox4) protect pancreatic cancer cells from apoptosis, and may play an important role in pancreaticcancer resistance to treatment and thus represent a novel therapeutic target. Expand
Up-regulation of hypoxia-inducible factors HIF-1α and HIF-2α under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function
TLDR
Evidence is provided for a role of the VHL protein in regulation of angiogenesis and erythropoiesis mediated by the HIF-1α and Hif-2α proteins. Expand
Reactive oxygen species from NAD(P)H:quinone oxidoreductase constitutively activate NF-κB in malignant melanoma cells
The transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in malignancies from enhanced activity of inhibitor of NF-kappaB (IkappaB) kinase, with accelerated IkappaBalphaExpand
Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases.
Reactive oxygen species (ROS) are important signal transduction molecules in ligand-induced signaling, regulation of cell growth, differentiation, apoptosis and motility. Recently NADPH oxidasesExpand
Two Novel Proteins Activate Superoxide Generation by the NADPH Oxidase NOX1*
TLDR
It is shown that NOX1 generates superoxide when co-expressed with the p47 phox and p67 phox subunits of the phagocyte NADPH oxidase but not when expressed by itself. Expand
...
1
2
3
4
...