By: Subhash Gangar
HIF-3 alpha (hypoxia-inducible factor 3-alpha/ HIF3A) represents an isoform of HIF-alpha subunits which heterodimerize with stable beta subunit (HIF-beta) for the regulation of HIF target genes through binding to hypoxia response elements/HRE in the promoter regions. HIF-3 alpha is the least studied member of HIF family but it is known to be regulated by HIF1 at the transcriptional level and it exerts inhibitory effects on HIF1 alpha or HIF-dependent gene regulation, in a cell-type specific manner. HIF‑3 alpha has a transcriptional regulatory function, which negatively affects the gene expression by competing with HIF-1 alpha and HIF-2 alpha in binding to transcriptional elements of target genes during hypoxia, and its role as transcription factor has been confirmed recently with the identification of HIF-3 alpha target genes (1). Several alternative HIF-3 alpha splicing variants have been reported but their precise biological function is not discovered well at the moment.
HIF-3 alpha Antibody [NB100-2529] – WB analysis of 30 ug lysates from human papillary renal cell carcinoma samples using HIF-3 alpha antibody at 1:1000 dilution with ON 4C incubation and detection via IRDye 800CW labelled secondary antibody on Odyssey Imaging System.
Li et al 2006 have reported that the hypoxia induces HIF-3 alpha expression in pulmonary alveolar epithelial cells and that it acts as complementary rather than redundant to HIF-1 alpha induction in protection against damage from hypoxic stress (2). Ando et al 2013 reported that one of the HIF-3 alpha splicing variants namely HIF-3 alpha-4 was silenced by the promoter DNA methylation in meningiomas, and the inducible HIF-3 alpha-4 protein repressed angiogenesis, cellular proliferation, and metabolism/oxidation in hypervascular meningiomas (3). Kumar et al 2015 documented that HIF-3 alpha plays a critical role in LPS induced inflammatory process in BV-2 microglia cells and by exploring the effect of NF-kB inhibitor PDTC on LPS-induced nuclear translocation of HIF-3 alpha, they demonstrated that HIF-3 alpha expression under inflammatory conditions is potentially directly regulated by NF-kB signaling (4). With their experiments involving pulmonary endothelial cells (PECs) isolated from HIF-3 alpha functional KO and WT adult mice, Kobayashi et al. 2015 recently reported that HIF-3 alpha tightly downregulates the expression of hypoxia-inducible angiogenic genes such as Tie2, VEGF R2/KDR/Flk-1 and Angiopoietin-2/Ang2 independent of the oxygen levels and of HIF-2 alpha as well as Ets-1, and they proposed that HIF-3 alpha enhances the angiogenic activity of PECs via repression of VE-cadherin protein which is a well-established inhibitor of Flk1/PI3 kinase/Akt signaling (5).
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