Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein

O Iliopoulos, A P Levy, C Jiang, W G Kaelin Jr, M A Goldberg, O Iliopoulos, A P Levy, C Jiang, W G Kaelin Jr, M A Goldberg

Abstract

Inactivation of the von Hippel-Lindau protein (pVHL) has been implicated in the pathogenesis of renal carcinomas and central nervous system hemangioblastomas. These are highly vascular tumors which overproduce angiogenic peptides such as vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Renal carcinoma cells lacking wild-type pVHL were found to produce mRNAs encoding VEGF/VPF, the glucose transporter GLUT1, and the platelet-derived growth factor B chain under both normoxic and hypoxic conditions. Reintroduction of wild-type, but not mutant, pVHL into these cells specifically inhibited the production of these mRNAs under normoxic conditions, thus restoring their previously described hypoxia-inducible profile. Thus, pVHL appears to play a critical role in the transduction of signals generated by changes in ambient oxygen tension.

References

    1. Ann Intern Med. 1981 Jul;95(1):71-87
    1. Growth Factors. 1995;12(4):289-301
    1. Cell. 1988 Jul 15;54(2):275-83
    1. Science. 1988 Dec 9;242(4884):1412-5
    1. J Clin Invest. 1990 Aug;86(2):670-4
    1. Am J Physiol. 1992 Mar;262(3 Pt 1):C682-90
    1. Am J Physiol. 1992 Aug;263(2 Pt 1):C326-33
    1. Nature. 1992 Oct 29;359(6398):843-5
    1. Nature. 1993 Apr 29;362(6423):841-4
    1. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1234-41
    1. J Biol Chem. 1994 Feb 11;269(6):4355-9
    1. Nature. 1994 Feb 10;367(6463):576-9
    1. Cancer Res. 1994 Aug 1;54(15):4233-7
    1. Cancer Res. 1994 Sep 15;54(18):4845-7
    1. Nat Genet. 1994 May;7(1):85-90
    1. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4
    1. Am J Hum Genet. 1994 Dec;55(6):1092-102
    1. JAMA. 1995 Feb 15;273(7):564-70
    1. Tohoku J Exp Med. 1994 Jul;173(3):355-60
    1. Hum Mol Genet. 1994 Dec;3(12):2169-73
    1. Cancer Res. 1995 Mar 15;55(6):1358-64
    1. Circ Res. 1995 May;76(5):758-66
    1. J Biol Chem. 1995 Jun 2;270(22):13333-40
    1. Circ Res. 1995 Sep;77(3):638-43
    1. J Biol Chem. 1995 Aug 25;270(34):19761-6
    1. FEBS Lett. 1995 Aug 21;370(3):203-8
    1. Science. 1995 Sep 8;269(5229):1402-6
    1. Science. 1995 Sep 8;269(5229):1439-43
    1. Science. 1995 Sep 8;269(5229):1444-6
    1. Mol Cell Biol. 1995 Oct;15(10):5363-8
    1. Breast Cancer Res Treat. 1995;36(2):139-55
    1. Nat Med. 1995 Aug;1(8):822-6
    1. Mol Med. 1995 Jan;1(2):182-93
    1. J Biol Chem. 1996 Feb 2;271(5):2746-53
    1. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10589-94
    1. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7972-6

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다