FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000699462> ?p ?o ?g. }

• W2000699462 endingPage "21267" @default.
• W2000699462 startingPage "21262" @default.
• W2000699462 abstract "To identify new dimerization partners for the aromatic hydrocarbon receptor nuclear translocator (Arnt), we used its N-terminal region (amino acids 1-470) as a target in a two-hybrid screening procedure, and we cloned the murine form of hypoxia-inducible factor 1α (HIF1α). Sequence comparisons reveal substantial identity between mouse and human HIF1α. Hypoxia induces a 10-fold accumulation of phosphoglycerate kinase 1 mRNA in wild type mouse hepatoma (Hepa 1c1c7) cells; the induction mechanism is Arnt dependent because induction does not occur in Arnt-defective cells. Furthermore, induction of phosphoglycerate kinase 1 mRNA requires Arnt's N-terminal region, which mediates DNA binding and heterodimerization; in contrast, induction does not require Arnt's C-terminal region, which mediates transactivation. We also show that a GAL4-HIF1α fusion protein transactivates a GAL4-dependent gene in the absence of Arnt, that HIF1α's transactivation capability is inducible by hypoxia, and that both hypoxia responsiveness and transactivation capability reside within the C-terminal 83 amino acids of HIF1α. Our findings generate new insights into the mechanism by which Arnt and HIF1α induce transcription in response to hypoxia. To identify new dimerization partners for the aromatic hydrocarbon receptor nuclear translocator (Arnt), we used its N-terminal region (amino acids 1-470) as a target in a two-hybrid screening procedure, and we cloned the murine form of hypoxia-inducible factor 1α (HIF1α). Sequence comparisons reveal substantial identity between mouse and human HIF1α. Hypoxia induces a 10-fold accumulation of phosphoglycerate kinase 1 mRNA in wild type mouse hepatoma (Hepa 1c1c7) cells; the induction mechanism is Arnt dependent because induction does not occur in Arnt-defective cells. Furthermore, induction of phosphoglycerate kinase 1 mRNA requires Arnt's N-terminal region, which mediates DNA binding and heterodimerization; in contrast, induction does not require Arnt's C-terminal region, which mediates transactivation. We also show that a GAL4-HIF1α fusion protein transactivates a GAL4-dependent gene in the absence of Arnt, that HIF1α's transactivation capability is inducible by hypoxia, and that both hypoxia responsiveness and transactivation capability reside within the C-terminal 83 amino acids of HIF1α. Our findings generate new insights into the mechanism by which Arnt and HIF1α induce transcription in response to hypoxia. INTRODUCTIONThe aromatic hydrocarbon receptor nuclear translocator (Arnt) 1The abbreviations used are: ArntAhR nuclear translocatorAhRaromatic hydrocarbon receptorHIF1αhypoxia-inducible factor 1αCATchloramphenicol acetyltransferasePGK1phosphoglycerate kinase 1PCRpolymerase chain reactionkbkilobasebHLHbasic helix-loop-helix. was first identified and characterized as a component of a heterodimeric, DNA-binding protein that regulates cytochrome P4501A1 (CYP1A1) transcription in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar, 2Hoffman E.C. Reyes H. Chu F-F. Sander F. Conley L.H. Brooks B.A. Hankinson O. Science. 1991; 252: 954-958Google Scholar, 3Reyes H. Reisz-Porszasz S. Hankinson O. Science. 1992; 256: 1193-1195Google Scholar). Induction of CYP1A1 gene expression by dioxin involves the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to its intracellular target, the aromatic hydrocarbon receptor (AhR) (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar, 4Burbach K.M. Poland A. Bradfield C.A. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 8185-8189Google Scholar, 5Ema M.K. Sogawa N. Watanabe Y. Chujoh N. Matsushita N. Gotoh O. Funae Y. Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 1992; 184: 246-253Google Scholar, 6Okey A.B. Riddick D.S. Harper P.A. Trends Pharmacol. Sci. 1994; 15: 226-232Google Scholar, 7Swanson H.I. Bradfield C.A. Pharmacogenetics. 1993; 3: 213-230Google Scholar). The liganded AhR enters the nucleus, where it interacts with Arnt, generating an AhR/Arnt heterodimer that recognizes a specific nucleotide sequence within an enhancer upstream of the CYP1A1 gene (8Fisher J.M. Wu L. Denison M.S. Whitlock Jr., J.P. J. Biol. Chem. 1990; 265: 9676-9681Google Scholar, 9Probst M.R. Reisz-Porszasz S. Abunag V. Ong M.S. Hankinson O. Mol. Pharmacol. 1993; 44: 511-518Google Scholar, 10Whitelaw M. Pongratz I. Wilhelmsson A. Gustafsson J.-A. Poellinger L. Mol. Cell. Biol. 1993; 13: 2504-2514Google Scholar, 11Whitlock Jr., J.P. Chem. Res. Toxicol. 1993; 6: 754-763Google Scholar). The binding of AhR/Arnt to the enhancer induces transcription, which is accompanied by alterations in chromatin structure and the binding of general transcription factors to the CYP1A1 promoter (12Ko H.P. Okino S.T. Ma Q. Whitlock Jr., J.P. Mol. Cell. Biol. 1996; 16: 430-436Google Scholar, 13Okino S.T. Whitlock Jr., J.P. Mol. Cell. Biol. 1995; 15: 3714-3721Google Scholar, 14Whitlock Jr., J.P. Okino S.T. Dong L. Ko H.P. Clarke-Katzenberg R. Ma Q. Li H. FASEB J. 1996; 10: 809-818Google Scholar). Induction of cytochrome P4501A1 enzyme activity increases the ability of the cell to detoxify aromatic hydrocarbons (15Conney A.H. Cancer Res. 1982; 42: 4875-4917Google Scholar). Thus, induction represents an interesting mechanism by which the cell adapts to changes in its external environment.As is typical of many transcription factors, AhR and Arnt have modular organizations. For example, both AhR and Arnt contain basic helix-loop-helix (bHLH) motifs; the HLH domains mediate heterodimerization between AhR and Arnt, while the basic regions are responsible for the binding of the AhR/Arnt heterodimer to DNA (16Dong L. Ma Q. Whitlock Jr., J.P. J. Biol. Chem. 1996; 271: 7942-7948Google Scholar, 17Fukunaga B.N. Probst M.R. Reisz-Porszasz S. Hankinson O. J. Biol. Chem. 1995; 270: 29270-29278Google Scholar, 18Reisz-Porszasz S. Probst M.R. Fukunaga B.N. Hankinson O. Mol. Cell. Biol. 1994; 14: 6075-6086Google Scholar). Both AhR and Arnt exhibit regions of amino acid sequence homology with Per (a Drosophila circadian rhythm protein) and Sim (a protein involved in Drosophila central nervous system development) (19Huang Z.J. Edery I. Robash M. Nature. 1993; 364: 259-263Google Scholar, 20Nambu J.R. Lewis J.O. Wharton K.A. Crews S.T. Cell. 1991; 67: 1157-1167Google Scholar). These regions of homology (PAS domains) may contribute to protein-protein interactions during heterodimerization (18Reisz-Porszasz S. Probst M.R. Fukunaga B.N. Hankinson O. Mol. Cell. Biol. 1994; 14: 6075-6086Google Scholar, 21Lindebro M.C. Poellinger L. Whitelaw M.L. EMBO J. 1995; 14: 3528-3539Google Scholar). In addition, AhR and Arnt have transactivation domains, which are functionally distinct from the DNA-binding and heterodimerization domains (22Jain S. Dolwick K.M. Schmidt J.V. Bradfield C.A. J. Biol. Chem. 1994; 269: 31518-31524Google Scholar, 23Li H. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1994; 269: 28098-28105Google Scholar, 24Ma Q. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1995; 270: 12697-12703Google Scholar, 25Sogawa K. Iwabuchi K. Abe H. Fujii-Kuriyama Y. J. Cancer Res. Clin. Oncol. 1995; 121: 612-620Google Scholar, 26Whitelaw M.L. Gustafsson J-A. Poellinger L. Mol. Cell. Biol. 1994; 14: 8343-8355Google Scholar).Others (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar) have suggested that Arnt might play a more general role in mediating cellular responses to environmental stimuli and, therefore, that cells might contain additional proteins that serve as heterodimerization partners for Arnt. In support of this idea, studies of human hypoxia-inducible factor 1, which regulates cellular responses to low oxygen tension, reveal that it contains two bHLH/PAS proteins, hypoxia-inducible factor 1α (HIF1α) and Arnt (27Wang G.L. Jiang B.H. Rue E.A. Semenza G.L. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 5510-5514Google Scholar). Such findings raise the intriguing possibility that cellular adaptation to hypoxia involves a mechanism that is Arnt dependent. Arnt could be very influential in such a role because adaptation to hypoxia involves increases in erythropoiesis, vascularization, and glycolytic enzyme activity, as well as other changes (28Goldberg M.A. Schneider T.J. J. Biol. Chem. 1994; 269: 4355-4359Google Scholar, 29Helfman T. Falanga V. Am. J. Med. Sci. 1993; 306: 37-41Google Scholar, 30Semenza G.L. Roth P.H. Fang H.-M. Wang G.L. J. Biol. Chem. 1994; 269: 23757-23763Google Scholar, 31Wenger R.H. Rolfs A. Marti H.H. Bauer C. Gassman M. J. Biol. Chem. 1995; 270: 27865-27870Google Scholar).We have undertaken a two-hybrid screening approach to find new proteins that interact with Arnt. We have used as the target Arnt's N-terminal region, which participates in Arnt's protein-protein interactions with AhR. Using this approach, we have identified mouse HIF1α as a heterodimerization partner for mouse Arnt. We demonstrate the functional importance of this observation by showing that Arnt is required for induction of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) in response to hypoxia. Our studies provide new insights into the mechanism by which cells adapt to low oxygen tension, and they emphasize the importance of Arnt as a regulator of cellular responses to environmental stimuli.DISCUSSIONWe have used a yeast two-hybrid system to clone and identify mouse HIF1α as a dimerization partner for mouse Arnt. The functional importance of this protein-protein interaction is revealed by our observation that the PGK1 gene fails to respond to hypoxia in Arnt-defective cells. Our findings complement and extend those of Wang et al. (27Wang G.L. Jiang B.H. Rue E.A. Semenza G.L. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 5510-5514Google Scholar) and Wang and Semenza (41Wang G.L. Semenza G.L. J. Biol. Chem. 1995; 270: 1230-1237Google Scholar), who identified HIF1α and Arnt as components of a DNA-binding protein complex that mediates cellular responses to hypoxia in human cells. The high amino acid sequence homology between mouse and human HIF1α suggests that the regulatory mechanism by which cells adapt to low oxygen tension is similar for the two species.Two observations imply that Arnt's HLH domain is important for its interaction with HIF1α. First, successful cloning relied upon a protein-protein interaction between HIF1α and a fragment of Arnt that contains its bHLH and PAS domains, which have been implicated in Arnt's heterodimerization capability. Second, deletion of Arnt's bHLH domain abrogates the response of the PGK1 gene to oxygen deprivation. The simplest explanation for this finding is that ArntΔbHLH fails to heterodimerize with HIF1α.Our findings indicate that Arnt's transactivation domain is dispensable for the induction of PGK1 gene expression by hypoxia. Similarly, we reported previously that Arnt's transactivation capability is not required for the induction of CYP1A1 transcription by dioxin (12Ko H.P. Okino S.T. Ma Q. Whitlock Jr., J.P. Mol. Cell. Biol. 1996; 16: 430-436Google Scholar). Therefore, in both the hypoxia-responsive and dioxin-responsive systems, Arnt appears to serve as a dimerization partner that confers DNA recognition capability upon HIF1α/Arnt and AhR/Arnt, respectively.Studies of dioxin-inducible transcription reveal that AhR/Arnt binds to the consensus DNA sequence 5′-TNGCGTG-3′ in the CYP1A1 enhancer (42Lusska A. Shen E. Whitlock Jr., J.P. J. Biol. Chem. 1993; 268: 6575-6580Google Scholar, 43Shen E.S. Whitlock Jr., J.P. J. Biol. Chem. 1992; 267: 6815-6819Google Scholar). Cross-linking studies and binding site selection experiments suggest that Arnt's basic domain binds to the 5′-GTG-3′ component of the CYP1A1 consensus sequence (37Swanson H.I. Chan W.K. Bradfield C.A. J. Biol. Chem. 1995; 270: 26292-26302Google Scholar, 44Bacsi S.G. Reisz-Porszasz S. Hankinson O. Mol. Pharmacol. 1995; 47: 432-438Google Scholar). By comparison, studies of hypoxia-responsive genes imply that HIF1α/Arnt recognizes the consensus DNA sequence 5′-(G/Y)ACGTGC(G/T)-3′ upstream of PGK1 (30Semenza G.L. Roth P.H. Fang H.-M. Wang G.L. J. Biol. Chem. 1994; 269: 23757-23763Google Scholar). We note that this nucleotide sequence also contains a 5′-GTG-3′ motif; we speculate that it interacts with Arnt's basic domain during the induction of PGK1 transcription by hypoxia. We also note that AhR/Arnt's recognition sequence and HIF1α/Arnt's recognition sequence both contain a CpG dinucleotide, a motif that may undergo cytosine methylation. Cytosine methylation blocks the binding of AhR/Arnt to its recognition sequence and the response to dioxin (45Shen E.S. Whitlock Jr., J.P. J. Biol. Chem. 1989; 264: 17754-17758Google Scholar). By analogy, we envision that cytosine methylation may also block DNA binding by HIF1α/Arnt and the response to hypoxia. Thus, we hypothesize that DNA methylation has the potential to inhibit some cellular responses to decreased oxygen tension, possibly in tissue-specific fashion.Our findings indicate that HIF1α and AhR differ with respect to their transactivation mechanisms. In particular, we show that HIF1α's transactivation function is expressed independently of Arnt; however, in the dioxin-responsive system, transactivation by AhR requires heterodimerization with Arnt. We envision that heterodimerization triggers a conformational change in AhR, which allows its latent transactivation function to be expressed (12Ko H.P. Okino S.T. Ma Q. Whitlock Jr., J.P. Mol. Cell. Biol. 1996; 16: 430-436Google Scholar, 24Ma Q. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1995; 270: 12697-12703Google Scholar). Transactivation by HIF1α must involve a different mechanism because it does not require Arnt for expression.In several other receptor-dependent regulatory systems (i.e. those that respond to glucocorticoid hormones, heat shock, or dioxin), the receptor domain that mediates inducibility is distinct from the domain that mediates transactivation (24Ma Q. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1995; 270: 12697-12703Google Scholar, 46Beato M. Herrlich P. Schütz G. Cell. 1995; 83: 851-857Google Scholar, 47Green M. Scheutz Sullivan E.K. Kingston R.E. Mol. Cell. Biol. 1995; 15: 3354-3362Google Scholar). Thus, the observation that hypoxia responsiveness and transactivation capability map to the same 83-amino acid region of HIF1α is unusual because it suggests that the functional domains are congruent. Its amino acid composition and primary sequence reveal that HIF1α's C-terminal 83-amino acid segment is not rich in acidic residues, glutamine, or proline; thus, it does not resemble certain transactivation domains described previously (40Tjian R. Maniatis T. Cell. 1994; 77: 5-8Google Scholar). The segment is enriched in leucine and isoleucine residues (∼20%), as well as in serine residues (∼11%), and it exhibits clusters of hydrophilic and hydrophobic amino acids. These atypical properties may reflect the fact that the segment mediates hypoxia responsiveness as well as transactivation and, therefore, that its structure reflects a combination of these two functions.The fact that Arnt is a component of more than one regulatory pathway is interesting for several reasons. First, it increases the plausibility that Arnt mediates additional adaptive responses to environmental stimuli and that other Arnt-dependent signaling systems exist within the cell. Second, it raises the possibility that “cross-talk” exists between Arnt-dependent regulatory systems and that activation of one pathway (e.g. by dioxin) may affect the cell's ability to respond to a second stimulus (e.g. hypoxia). These appear to be potentially interesting issues for future research. INTRODUCTIONThe aromatic hydrocarbon receptor nuclear translocator (Arnt) 1The abbreviations used are: ArntAhR nuclear translocatorAhRaromatic hydrocarbon receptorHIF1αhypoxia-inducible factor 1αCATchloramphenicol acetyltransferasePGK1phosphoglycerate kinase 1PCRpolymerase chain reactionkbkilobasebHLHbasic helix-loop-helix. was first identified and characterized as a component of a heterodimeric, DNA-binding protein that regulates cytochrome P4501A1 (CYP1A1) transcription in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar, 2Hoffman E.C. Reyes H. Chu F-F. Sander F. Conley L.H. Brooks B.A. Hankinson O. Science. 1991; 252: 954-958Google Scholar, 3Reyes H. Reisz-Porszasz S. Hankinson O. Science. 1992; 256: 1193-1195Google Scholar). Induction of CYP1A1 gene expression by dioxin involves the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to its intracellular target, the aromatic hydrocarbon receptor (AhR) (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar, 4Burbach K.M. Poland A. Bradfield C.A. Proc. Natl. Acad. Sci. U. S. A. 1992; 89: 8185-8189Google Scholar, 5Ema M.K. Sogawa N. Watanabe Y. Chujoh N. Matsushita N. Gotoh O. Funae Y. Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 1992; 184: 246-253Google Scholar, 6Okey A.B. Riddick D.S. Harper P.A. Trends Pharmacol. Sci. 1994; 15: 226-232Google Scholar, 7Swanson H.I. Bradfield C.A. Pharmacogenetics. 1993; 3: 213-230Google Scholar). The liganded AhR enters the nucleus, where it interacts with Arnt, generating an AhR/Arnt heterodimer that recognizes a specific nucleotide sequence within an enhancer upstream of the CYP1A1 gene (8Fisher J.M. Wu L. Denison M.S. Whitlock Jr., J.P. J. Biol. Chem. 1990; 265: 9676-9681Google Scholar, 9Probst M.R. Reisz-Porszasz S. Abunag V. Ong M.S. Hankinson O. Mol. Pharmacol. 1993; 44: 511-518Google Scholar, 10Whitelaw M. Pongratz I. Wilhelmsson A. Gustafsson J.-A. Poellinger L. Mol. Cell. Biol. 1993; 13: 2504-2514Google Scholar, 11Whitlock Jr., J.P. Chem. Res. Toxicol. 1993; 6: 754-763Google Scholar). The binding of AhR/Arnt to the enhancer induces transcription, which is accompanied by alterations in chromatin structure and the binding of general transcription factors to the CYP1A1 promoter (12Ko H.P. Okino S.T. Ma Q. Whitlock Jr., J.P. Mol. Cell. Biol. 1996; 16: 430-436Google Scholar, 13Okino S.T. Whitlock Jr., J.P. Mol. Cell. Biol. 1995; 15: 3714-3721Google Scholar, 14Whitlock Jr., J.P. Okino S.T. Dong L. Ko H.P. Clarke-Katzenberg R. Ma Q. Li H. FASEB J. 1996; 10: 809-818Google Scholar). Induction of cytochrome P4501A1 enzyme activity increases the ability of the cell to detoxify aromatic hydrocarbons (15Conney A.H. Cancer Res. 1982; 42: 4875-4917Google Scholar). Thus, induction represents an interesting mechanism by which the cell adapts to changes in its external environment.As is typical of many transcription factors, AhR and Arnt have modular organizations. For example, both AhR and Arnt contain basic helix-loop-helix (bHLH) motifs; the HLH domains mediate heterodimerization between AhR and Arnt, while the basic regions are responsible for the binding of the AhR/Arnt heterodimer to DNA (16Dong L. Ma Q. Whitlock Jr., J.P. J. Biol. Chem. 1996; 271: 7942-7948Google Scholar, 17Fukunaga B.N. Probst M.R. Reisz-Porszasz S. Hankinson O. J. Biol. Chem. 1995; 270: 29270-29278Google Scholar, 18Reisz-Porszasz S. Probst M.R. Fukunaga B.N. Hankinson O. Mol. Cell. Biol. 1994; 14: 6075-6086Google Scholar). Both AhR and Arnt exhibit regions of amino acid sequence homology with Per (a Drosophila circadian rhythm protein) and Sim (a protein involved in Drosophila central nervous system development) (19Huang Z.J. Edery I. Robash M. Nature. 1993; 364: 259-263Google Scholar, 20Nambu J.R. Lewis J.O. Wharton K.A. Crews S.T. Cell. 1991; 67: 1157-1167Google Scholar). These regions of homology (PAS domains) may contribute to protein-protein interactions during heterodimerization (18Reisz-Porszasz S. Probst M.R. Fukunaga B.N. Hankinson O. Mol. Cell. Biol. 1994; 14: 6075-6086Google Scholar, 21Lindebro M.C. Poellinger L. Whitelaw M.L. EMBO J. 1995; 14: 3528-3539Google Scholar). In addition, AhR and Arnt have transactivation domains, which are functionally distinct from the DNA-binding and heterodimerization domains (22Jain S. Dolwick K.M. Schmidt J.V. Bradfield C.A. J. Biol. Chem. 1994; 269: 31518-31524Google Scholar, 23Li H. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1994; 269: 28098-28105Google Scholar, 24Ma Q. Dong L. Whitlock Jr., J.P. J. Biol. Chem. 1995; 270: 12697-12703Google Scholar, 25Sogawa K. Iwabuchi K. Abe H. Fujii-Kuriyama Y. J. Cancer Res. Clin. Oncol. 1995; 121: 612-620Google Scholar, 26Whitelaw M.L. Gustafsson J-A. Poellinger L. Mol. Cell. Biol. 1994; 14: 8343-8355Google Scholar).Others (1Hankinson O. Annu. Rev. Pharmacol. Toxicol. 1995; 35: 307-340Google Scholar) have suggested that Arnt might play a more general role in mediating cellular responses to environmental stimuli and, therefore, that cells might contain additional proteins that serve as heterodimerization partners for Arnt. In support of this idea, studies of human hypoxia-inducible factor 1, which regulates cellular responses to low oxygen tension, reveal that it contains two bHLH/PAS proteins, hypoxia-inducible factor 1α (HIF1α) and Arnt (27Wang G.L. Jiang B.H. Rue E.A. Semenza G.L. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 5510-5514Google Scholar). Such findings raise the intriguing possibility that cellular adaptation to hypoxia involves a mechanism that is Arnt dependent. Arnt could be very influential in such a role because adaptation to hypoxia involves increases in erythropoiesis, vascularization, and glycolytic enzyme activity, as well as other changes (28Goldberg M.A. Schneider T.J. J. Biol. Chem. 1994; 269: 4355-4359Google Scholar, 29Helfman T. Falanga V. Am. J. Med. Sci. 1993; 306: 37-41Google Scholar, 30Semenza G.L. Roth P.H. Fang H.-M. Wang G.L. J. Biol. Chem. 1994; 269: 23757-23763Google Scholar, 31Wenger R.H. Rolfs A. Marti H.H. Bauer C. Gassman M. J. Biol. Chem. 1995; 270: 27865-27870Google Scholar).We have undertaken a two-hybrid screening approach to find new proteins that interact with Arnt. We have used as the target Arnt's N-terminal region, which participates in Arnt's protein-protein interactions with AhR. Using this approach, we have identified mouse HIF1α as a heterodimerization partner for mouse Arnt. We demonstrate the functional importance of this observation by showing that Arnt is required for induction of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) in response to hypoxia. Our studies provide new insights into the mechanism by which cells adapt to low oxygen tension, and they emphasize the importance of Arnt as a regulator of cellular responses to environmental stimuli." @default.
• W2000699462 created "2016-06-24" @default.
• W2000699462 creator A5052519997 @default.
• W2000699462 creator A5078478049 @default.
• W2000699462 creator A5083534218 @default.
• W2000699462 date "1996-08-01" @default.
• W2000699462 modified "2023-10-01" @default.
• W2000699462 title "Induction of Phosphoglycerate Kinase 1 Gene Expression by Hypoxia" @default.
• W2000699462 cites W1482333001 @default.
• W2000699462 cites W1485553398 @default.
• W2000699462 cites W1486593521 @default.
• W2000699462 cites W1503667331 @default.
• W2000699462 cites W1536635467 @default.
• W2000699462 cites W1544237631 @default.
• W2000699462 cites W1561943947 @default.
• W2000699462 cites W1591714400 @default.
• W2000699462 cites W1600605923 @default.
• W2000699462 cites W1605083411 @default.
• W2000699462 cites W1656100325 @default.
• W2000699462 cites W1748456144 @default.
• W2000699462 cites W1826000501 @default.
• W2000699462 cites W1876406296 @default.
• W2000699462 cites W1969656285 @default.
• W2000699462 cites W1971494855 @default.
• W2000699462 cites W1973912514 @default.
• W2000699462 cites W1977186059 @default.
• W2000699462 cites W1980214543 @default.
• W2000699462 cites W1980678647 @default.
• W2000699462 cites W1982265633 @default.
• W2000699462 cites W1987183940 @default.
• W2000699462 cites W1990260467 @default.
• W2000699462 cites W1990874048 @default.
• W2000699462 cites W1996454474 @default.
• W2000699462 cites W1999087731 @default.
• W2000699462 cites W2009225735 @default.
• W2000699462 cites W2017133589 @default.
• W2000699462 cites W2018058963 @default.
• W2000699462 cites W2024206845 @default.
• W2000699462 cites W2037489737 @default.
• W2000699462 cites W2064209430 @default.
• W2000699462 cites W2077945512 @default.
• W2000699462 cites W2082584138 @default.
• W2000699462 cites W2084880501 @default.
• W2000699462 cites W2085609942 @default.
• W2000699462 cites W2087332917 @default.
• W2000699462 cites W2107038109 @default.
• W2000699462 cites W2128673805 @default.
• W2000699462 cites W2129185784 @default.
• W2000699462 cites W2146909058 @default.
• W2000699462 cites W2169539585 @default.
• W2000699462 cites W4237567990 @default.
• W2000699462 doi "https://doi.org/10.1074/jbc.271.35.21262" @default.
• W2000699462 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8702901" @default.
• W2000699462 hasPublicationYear "1996" @default.
• W2000699462 type Work @default.
• W2000699462 sameAs 2000699462 @default.
• W2000699462 citedByCount "152" @default.
• W2000699462 countsByYear W20006994622012 @default.
• W2000699462 countsByYear W20006994622013 @default.
• W2000699462 countsByYear W20006994622014 @default.
• W2000699462 countsByYear W20006994622015 @default.
• W2000699462 countsByYear W20006994622016 @default.
• W2000699462 countsByYear W20006994622017 @default.
• W2000699462 countsByYear W20006994622019 @default.
• W2000699462 countsByYear W20006994622020 @default.
• W2000699462 countsByYear W20006994622021 @default.
• W2000699462 countsByYear W20006994622022 @default.
• W2000699462 countsByYear W20006994622023 @default.
• W2000699462 crossrefType "journal-article" @default.
• W2000699462 hasAuthorship W2000699462A5052519997 @default.
• W2000699462 hasAuthorship W2000699462A5078478049 @default.
• W2000699462 hasAuthorship W2000699462A5083534218 @default.
• W2000699462 hasBestOaLocation W20006994621 @default.
• W2000699462 hasConcept C104317684 @default.
• W2000699462 hasConcept C150194340 @default.
• W2000699462 hasConcept C153911025 @default.
• W2000699462 hasConcept C155911427 @default.
• W2000699462 hasConcept C178790620 @default.
• W2000699462 hasConcept C181199279 @default.
• W2000699462 hasConcept C184235292 @default.
• W2000699462 hasConcept C185592680 @default.
• W2000699462 hasConcept C20251656 @default.
• W2000699462 hasConcept C540031477 @default.
• W2000699462 hasConcept C55493867 @default.
• W2000699462 hasConcept C7836513 @default.
• W2000699462 hasConcept C86803240 @default.
• W2000699462 hasConcept C95444343 @default.
• W2000699462 hasConceptScore W2000699462C104317684 @default.
• W2000699462 hasConceptScore W2000699462C150194340 @default.
• W2000699462 hasConceptScore W2000699462C153911025 @default.
• W2000699462 hasConceptScore W2000699462C155911427 @default.
• W2000699462 hasConceptScore W2000699462C178790620 @default.
• W2000699462 hasConceptScore W2000699462C181199279 @default.
• W2000699462 hasConceptScore W2000699462C184235292 @default.
• W2000699462 hasConceptScore W2000699462C185592680 @default.
• W2000699462 hasConceptScore W2000699462C20251656 @default.
• W2000699462 hasConceptScore W2000699462C540031477 @default.
• W2000699462 hasConceptScore W2000699462C55493867 @default.

• next