Hypoxia-inducible factor 3-alpha

Definition:

Acts as a transcriptional regulator in adaptive response to low oxygen tension. Acts as a regulator of hypoxia-inducible gene expression. Functions as an inhibitor of angiogenesis in hypoxic cells of the cornea. Plays a role in the development of the cardiorespiratory system. May also be involved in apoptosis (By similarity).; [Isoform 2]: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. Also inhibits hypoxia-inducible ARNT-mediated gene expression.; [Isoform 3]: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.; [Isoform 4]: Attenuates the ability of transcription factor HIF1A and EPAS1/HIF2A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation. May act as a tumor suppressor and inhibits malignant cell transformation.; [Isoform 5]: Attenuates the ability of transcription factor HIF1A to bind to hypoxia-responsive elements (HRE) located within the enhancer/promoter of hypoxia-inducible target genes and hence inhibits HRE-driven transcriptional activation.

References:

[1]. Mindy A Maynard, et al. Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. Cell Cycle. 2007 Nov 15;6(22):2810-6. [Content Brief]

[2]. Mindy A Maynard, et al. Human HIF-3alpha4 is a dominant-negative regulator of HIF-1 and is down-regulated in renal cell carcinoma. FASEB J. 2005 Sep;19(11):1396-406. [Content Brief]

[3]. Tetsuhiro Tanaka, et al. The human HIF (hypoxia-inducible factor)-3alpha gene is a HIF-1 target gene and may modulate hypoxic gene induction. Biochem J. 2009 Oct 23;424(1):143-51. [Content Brief]

[4]. Antje Augstein, et al. Cell-specific and hypoxia-dependent regulation of human HIF-3α: inhibition of the expression of HIF target genes in vascular cells. Cell Mol Life Sci. 2011 Aug;68(15):2627-42. [Content Brief]

[5]. S Hara, et al. Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha. Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13. [Content Brief]

[6]. Annika Pasanen, et al. Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2. Int J Biochem Cell Biol. 2010 Jul;42(7):1189-200. [Content Brief]

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