Hypoxia inducible factor—la,

Huang J, Zhao Q, Mooney SM, Lee FS. Sequence determinants in hypoxia-inducible factor-la for hydroxylation by the prolyl hydroxylases PHDl, PHD2 and PHD3. J. Biol. Chem. 105. 2002 277 39792-39800. 

Page EL, Chan DA, Giaccia AJ, Levine M, Richard DE. Hypoxia-inducible factor-la stabilization in nonhypoxic condi- 111. tions role of oxidation and intracellular ascorbate depletion. Mol. 

Rosenberger C, Mandriota S, Jurgensen JS, Wiesener MS, Horstrup JH, Frei U, Ratcliffe PJ, Maxwell PH, Bachmann S, Eckardt K-U. Expression of hypoxia-inducible factor-la and -2a in hypoxic and ischemic rat kidneys. J. Am. Soc. Nephrol. 2002 13 1721-1732. 

Peyssonnaux C, Cejudo-Martin P, Doedens A, Zinkernagel AS, Johnson RS, Nizet V. Cutting edge essential role of hypoxia inducible factor-la in development of lipopolysaccharide-induced sepsis. J. Immunol. 2007 178 7516-7519. 

Hypoxia-Inducible Factor-la is a Necessary Mediator of the Pasteur Effect... 

Heat induction of the unphosphorylated form of hypoxia-inducible factor-la is dependent on heat shock protein-90 activity. J Biol Chem 277 9262-9267,... 

Katschinski DM, Le L, Schindler SG, Thomas T, Voss AK, et al. 2004. Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-la stabilization. Cell Physiol Biochem 14 351-360,... 

Page EL, Robitaille GA, Pouyssegur J, Richard DE. 2002. Induction of hypoxia-inducible factor-la by transcriptional and translational mechanisms. J Biol Chem 277 48403-48409. 

Richard DE, Berra E, Pouyssegur J. 2000. Nonhypoxic pathway mediates the induction of hypoxia-inducible factor la in vascular smooth muscle cells. J Biol Chem 275 26765-26771. 

Shams I, Avivi A, Nevo E. 2004. Hypoxic stress tolerance of the blind subterranean mole rat Expression of erythropoietin and hypoxia-inducible factor la. Proc Natl Acad Sci USA 101 9698-9703. 

Zhong H, De Marzo AM, Laughner E, et al. (1999) Overexpression of hypoxia-inducible factor-la in common human cancers and their metastases. Cancer Res 59 5830-5835... 

In human breast tumor cell lines, endothelins have been reported to induce CCR7 expression at both mRNA level and protein level through activation of endothelin receptor A (ET-RA) in a hypoxia-inducible factor-la (HIF-la)-dependent manner [40]. The endothelin system includes three small 21-amino acid peptides ligands (ET-1, ET-2, and ET-3), two G-protein-coupled receptors (ET-RA and ET-RB), and two activating peptidases [41]. Increased expression of endothelins and their receptors was found in invasive breast cancer compared to normal breast tissues or benign fibroadenomas [42, 43]. In human primary breast cancer, endothelin expression was correlated with CCR7 expression, both of which were associated with LN metastasis [40]. 

L.E. Huang, J. Gu, M. Schau, H.F. Bunn (1998). Regulation of hypoxia-inducible factor la is mediated by an oxygen dependent degradation domain via the ubiquitin proteasome pathway. Proc. Natl Acad. ScL U.S.A., 95, 7987-7992. 

Bos R, Zhong H, Hanrahan CF, Mommers E, Semenza GL, Pinedo HM, Abeloff MD, Simons JW, van Diest PJ, van der Wall E. Levels of hypoxia-inducible factor-la during breast carcinogenesis. J Natl Cancer Inst 2001 93 309-314. 

Trentin D, Hall H, Wechsler S, Hubbell JA, Peptide-matrix-mediated gene transfer of an oxygen-insensitive hypoxia-inducible factor-la variant for local induction of angiogenesis. Proc Natl Acad Sci USA, 2006, 103, 2506-11. 

Fig. 4.22. Hypoxia-mediated metabolic adaptation for energy preservation. Activation of genes for glucose transporter-1 (GLUT-1 = 1) and glycolytic enzymes yields an increased glycolytic rate. H -ions produced are preferentially exported via a Na /H -antiporter (NHE-1 = 3) and a lactate /H -symporter (monocarboxylate transporter MCT-1 = 2) leading to a drop in extracellular pH (pH.). Low extracellular pH activates the membrane-bound ectoenzyme carbonic anhydrase IX (CA IX = 4). Key mechanism regulating intracellular pH in tumor cells when protons are produced is also shown (Na -depen-dent HCOs" /CL -exchanger = 5). HIF-Ia = hypoxia-inducible factor la, PHDs = prolyl hydroxylases, FIH = asparagyl hydroxylase, lac" = lactic acid...

Kurebayashi J, Otsuki T, Moriya T, Sonoo H (2001) Hypoxia reduces hormone responsiveness of human breast cancer cells. Jpn J Cancer Res 92 1093-1101 Laderoute KR, Calaoagan JM, Gustafson-Brown C, Knapp AM, Li G-C, Mendonca HL, Ryan HE, Wang Z, Johnson RS (2002) The response of c-Jun/AP-1 to chronic hypoxia is hypoxia-inducible factor la dependent. Mol Cell Biol 22 2515-2523... 

Li B-Z, Zhuang W-Z, Oien P, Fu J-X (2008) Effects of RNA interference targeting hypoxia-inducible factor-la (HIF-la) on chemosensitivity of leukemia K562 cells towards homoharringtonine. Qiin J Cancer 27(7) 47-52... 

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