Role of HIf-1

The primary role of hypoxia inducing factor-1 (HIF-1) is transcriptional activation.  HIF-1 is a transcription factor that regulates hypoxia inducible genes [2,3].  Examples of hypoxia inducible genes are erythropoietin (EPO), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS),
heme oxygenase 1 (OH-1), aldolase A (ALDA), enolase 1 (ENO-1), glucose transporter 1(GLUT-1), lactate dehydrogenase A (LDHA), and phosphoglycerate kinase 1 (PGK-1) [4].
 
 
 

Function of HIF-1

As mentioned, earlier the HIF-1 is composed of an alpha and beta subunit.  The beta subunit is an aryl hydrocarbon receptor nuclear translocator (Arnt), and is needed for the function in the response to hypoxia [1].  The function of the alpha subunit is very important because it is a mediation of the response to hypoxia.  HIF-1 alpha protein is very unstable in cells exposed to oxygen, however hypoxia increases the abundance of HIF-1 alpha proteins[5].  Thus, the stabilization of HIF-1 alpha is needed to activate HIF-1.

HIF-1 activates genes that can be classified into three functional groups.

Group 1:

Proteins escalate tissue oxygen by the formation and development of erythrocytes (red blood cells).  Examples of these particular proteins are EPO and OH-1[2].

Group 2:

Proteins raise oxygen delivery to tissues through blood vessel relaxation and development.  Examples of these particular proteins are iNOS and VEGF [2].

Group 3:

Proteins, that in contrast to the two previous groups, do not alter the delivery of oxygen to tissues.  Instead, these proteins are necessary for the adaptation of cellular metabolism under conditions of low oxygen.  Examples of these proteins are GLUT-1 and most glycolytic enzymes [2].
 
 

References

[1]  Brody, Thomas B. "Hypoxia-inducible factor-1 (HIF-1), and Arnt-containing, heterodimeric basic
      helix-loop-helix transcription factor that regulates hypoxia-inducible genes" Evolutionary Homologs.
      1995, 1996

[2]  Chinmay K. Mukhopadhyay, Barsanjit Mazumder, and Paul L. Fox. "Role of Hypoxia-inducible
      Factor-1 in Transcriptional Activation of Ceruloplasmin by Iron Deficiency" Journal of Biol. Chem.,
      Vol.275, Issue 28, 21048-21054, July 14, 2000

[3]  V. Srinivas, X. Zhu, Susana Salceda, R. Nakamura, and Jamie Caro. "Hypoxia-inducible Factor 1
      Alpha (HIF-1 alpha) Is a Non-heme Iron Protein" The Journal of Biological Chemistry. Vol. 273
      No.29, Issue of July 17, pp.18019-18022, 1998

[4]  Kimura H, Weisz A, Ogura T, Hitomi Y, Kurashima Y, Hashimoto K, D'Acquisto F, Makuuchi M,
      Esumi H. "Identification of Hypoxia-Inducible Factor-1 (HIF-1) Ancillary Sequence and Its Function
      in Vascular Endothelial Growth Factor Gene Induction by Hypoxia and Nitric Oxide." The Journal of
     Biological Chemistry.  2000 Oct 30

[5]  L. Eric Huang, Jie Gu, Maureen Schau, and H. Franklin Bunn. "Regulation of hypoxia-inducible
      factor 1alpha is mediated by an O2 dependent degradation domain via the ubiquitin-proteasome
      pathway." Journal of Biochemistry. Vol. 95, Issue 14, 7987-7992, July 7, 1998