Hypoxia regulates the sperm associated antigen 4 (SPAG4) via HIF, which is expressed in renal clear cell carcinoma and promotes migration and invasion in vitro.

Hypoxia leads to the upregulation of a variety of genes mediated largely via the hypoxia inducible transcription factor (HIF). Prominent HIF-regulated target genes such as the vascular endothelial growth factor (VEGF), the glucose transporter 1 (Glut-1), or erythropoietin (EPO) help to assure survival of cells and organisms in a low oxygenated environment. Here, we are the first to report the hypoxic regulation of the sperm associated antigen 4 (SPAG4).

Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts.

The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control.

Deletion of the oxygen-dependent degradation domain results in impaired transcriptional activity of hypoxia-inducible factors.

Hypoxia-inducible factors (HIF1α/HIF2α) are key transcription factors that promote angiogenesis. The overexpression of degradation-resistant HIF mutants is considered a promising pro-angiogenic therapeutic tool. We compared the transcriptional activity of HIF1α/HIF2α mutants that obtained their resistance to oxygen-dependent degradation either by deletion of their entire oxygen-dependent degradation (ODD) domain or by replacement of prolyl residues that are crucial for oxygen-dependent degradation.

The GTPase RAB20 is a HIF target with mitochondrial localization mediating apoptosis in hypoxia.

Hypoxia is a common pathogenic stress, which requires adaptive activation of the Hypoxia-inducible transcription factor (HIF). In concert transcriptional HIF targets enhance oxygen availability and simultaneously reduce oxygen demand, enabling survival in a hypoxic microenvironment. Here, we describe the characterization of a new HIF-1 target gene, Rab20, which is a member of the Rab family of small GTP-binding proteins, regulating intracellular trafficking and vesicle formation.

The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1.

Hypoxia has been shown to promote tumor metastasis and lead to therapy resistance. Recent work has demonstrated that hypoxia represses E-cadherin expression, a hallmark of epithelial to mesenchymal transition, which is believed to amplify tumor aggressiveness. The molecular mechanism of E-cadherin repression is unknown, yet lysyl oxidases have been implicated to be involved.

HIF-1 or HIF-2 induction is sufficient to achieve cell cycle arrest in NIH3T3 mouse fibroblasts independent from hypoxia.

Hypoxia is a severe stress which induces physiological and molecular adaptations, where the latter is dominated by the Hypoxia-inducible transcription Factor (HIF). A well described response on cellular level upon exposure to hypoxia is a reversible cell cycle arrest, which probably renders the cells more resistant to the difficult environment. The individual roles of hypoxia itself and of the isoforms HIF-1alpha and HIF-2alpha in cell cycle regulation are poorly understood and discussed controversially.

The specific contribution of hypoxia-inducible factor-2alpha to hypoxic gene expression in vitro is limited and modulated by cell type-specific and exogenous factors.

Cellular integrity in hypoxia is dependent on molecular adaptations dominated by the heterodimeric transcription factor hypoxia-inducible factor (HIF). The HIF complex contains one of two alternative oxygen-regulated alpha-subunits considered to play distinct roles in the hypoxia response. Although HIF-2alpha may be more important in tumour biology and erythropoiesis, the spectrum of individual target genes is still insufficiently characterized.

Mutations in vimentin disrupt the cytoskeleton in fibroblasts and delay execution of apoptosis.

To get new insights into the function of the intermediate filament (IF) protein vimentin in cell physiology, we generated two mutant cDNAs, one with a point mutation in the consensus motif in coil1A (R113C) and one with the complete deletion of coil 2B of the rod domain. In keratins and glia filament protein (GFAP), analogous mutations cause keratinopathies and Alexander disease, respectively. Both mutants prevented filament assembly in vitro and inhibited assembly of wild-type vimentin when present in equal amounts.