Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension

G L Wang, B H Jiang, E A Rue, G L Semenza, G L Wang, B H Jiang, E A Rue, G L Semenza

Abstract

Hypoxia-inducible factor 1 (HIF-1) is found in mammalian cells cultured under reduced O2 tension and is necessary for transcriptional activation mediated by the erythropoietin gene enhancer in hypoxic cells. We show that both HIF-1 subunits are basic-helix-loop-helix proteins containing a PAS domain, defined by its presence in the Drosophila Per and Sim proteins and in the mammalian ARNT and AHR proteins. HIF-1 alpha is most closely related to Sim. HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. HIF-1 alpha and HIF-1 beta (ARNT) RNA and protein levels were induced in cells exposed to 1% O2 and decayed rapidly upon return of the cells to 20% O2, consistent with the role of HIF-1 as a mediator of transcriptional responses to hypoxia.

References

    1. J Biol Chem. 1993 Mar 25;268(9):6575-80
    1. Nature. 1992 Oct 29;359(6398):843-5
    1. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4304-8
    1. Nature. 1993 Jul 15;364(6434):259-62
    1. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8566-70
    1. J Biol Chem. 1993 Oct 15;268(29):21513-8
    1. Hum Mol Genet. 1993 Nov;2(11):1793-8
    1. J Biol Chem. 1994 Feb 11;269(6):4355-9
    1. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6496-500
    1. Mol Cell Biol. 1994 Sep;14(9):6075-86
    1. J Biol Chem. 1994 Sep 23;269(38):23757-63
    1. Cardiovasc Res. 1994 Aug;28(8):1176-9
    1. Mol Cell Biol. 1994 Dec;14(12):7984-95
    1. Development. 1994 Dec;120(12):3563-9
    1. J Biol Chem. 1995 Jan 20;270(3):1230-7
    1. Hematol Oncol Clin North Am. 1994 Oct;8(5):863-84
    1. Eur J Biochem. 1983 Oct 3;135(3):405-12
    1. J Mol Biol. 1985 May 5;183(1):1-12
    1. Cell. 1986 Aug 29;46(5):659-67
    1. Science. 1986 Oct 17;234(4774):364-8
    1. Nature. 1987 Mar 5-11;326(6108):42-7
    1. Nucleic Acids Res. 1987 Oct 26;15(20):8125-48
    1. Cell. 1988 Jan 15;52(1):143-51
    1. Science. 1988 Dec 9;242(4884):1412-5
    1. Cell. 1989 Aug 11;58(3):537-44
    1. J Bacteriol. 1989 Nov;171(11):6187-96
    1. J Mol Biol. 1990 Oct 5;215(3):403-10
    1. Cell. 1991 Feb 8;64(3):545-52
    1. Science. 1991 May 17;252(5008):954-8
    1. Cell. 1991 Dec 20;67(6):1157-67
    1. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):599-602
    1. Physiol Rev. 1992 Apr;72(2):449-89
    1. Science. 1992 May 22;256(5060):1193-5
    1. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8185-9
    1. Circ Res. 1992 Dec;71(6):1490-500
    1. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2423-7

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit