Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII)

Implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism

Massimo U. De Martino, Salvatore Alesci, George P. Chrousos, Tomoshige Kino

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Glucocorticoids exert their extremely diverse effects on numerous biologic activities of humans via only one protein module, the glucocorticoid receptor (GR). The GR binds to the glucocorticoid response elements located in the promoter region of target genes and regulates their transcriptional activity. In addition, GR associates with other transcription factors through direct protein-protein interactions and mutually represses or stimulates each other's transcriptional activities. The latter activity of GR may be more important than the former one, granted that mice harboring a mutant GR, which is active in terms of protein-protein interactions but inactive in terms of transactivation via DNA, survive and procreate, in contrast to mice with a deletion of the entire GR gene that die immediately after birth. We recently found that GR physically interacts with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays a critical role in the metabolism of glucose, cholesterol, and xenobiotics, as wel as in the development of the central nervous system in fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors, such as the silencing mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear receptor compressors (NCoRs) via its C-terminal domain. Their mutual interaction may play an important role in gluconeogenesis, lipoprotein metabolism, and enzymatic clearance of clinically important compounds and bioactive chemicals, by regulating their rate-limiting enzymes and molecules, including the phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A, and several apolipoproteins. It appears that glucocorticoids exert their intermediary effects partly via physical interaction with COUP-TFII.

Original languageEnglish
Pages (from-to)72-85
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume1024
DOIs
Publication statusPublished - 2004
Externally publishedYes

Fingerprint

COUP Transcription Factor II
Glucocorticoid Receptors
Xenobiotics
Metabolism
Glucocorticoids
Lipoproteins
Glucose
Proteins
Transcriptional Activation
Genes
Cholesterol 7-alpha-Hydroxylase
Transcription
Chicken
Interaction
Protein
Cytochrome P-450 CYP3A
Thyroid Hormone Receptors
Co-Repressor Proteins
Phosphoenolpyruvate
Gluconeogenesis

Keywords

  • Apolipoproteins
  • Cholesterol
  • Gluconeogenesis
  • P450 CYP3A
  • P450 CYP7A
  • Phosphoenolpyruvate carboxykinase (PEPCK)
  • Protein-protein interaction
  • Xenobiotic metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

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title = "Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): Implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism",
abstract = "Glucocorticoids exert their extremely diverse effects on numerous biologic activities of humans via only one protein module, the glucocorticoid receptor (GR). The GR binds to the glucocorticoid response elements located in the promoter region of target genes and regulates their transcriptional activity. In addition, GR associates with other transcription factors through direct protein-protein interactions and mutually represses or stimulates each other's transcriptional activities. The latter activity of GR may be more important than the former one, granted that mice harboring a mutant GR, which is active in terms of protein-protein interactions but inactive in terms of transactivation via DNA, survive and procreate, in contrast to mice with a deletion of the entire GR gene that die immediately after birth. We recently found that GR physically interacts with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays a critical role in the metabolism of glucose, cholesterol, and xenobiotics, as wel as in the development of the central nervous system in fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors, such as the silencing mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear receptor compressors (NCoRs) via its C-terminal domain. Their mutual interaction may play an important role in gluconeogenesis, lipoprotein metabolism, and enzymatic clearance of clinically important compounds and bioactive chemicals, by regulating their rate-limiting enzymes and molecules, including the phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A, and several apolipoproteins. It appears that glucocorticoids exert their intermediary effects partly via physical interaction with COUP-TFII.",
keywords = "Apolipoproteins, Cholesterol, Gluconeogenesis, P450 CYP3A, P450 CYP7A, Phosphoenolpyruvate carboxykinase (PEPCK), Protein-protein interaction, Xenobiotic metabolism",
author = "{De Martino}, {Massimo U.} and Salvatore Alesci and Chrousos, {George P.} and Tomoshige Kino",
year = "2004",
doi = "10.1196/annals.1321.006",
language = "English",
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T2 - Implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism

AU - De Martino, Massimo U.

AU - Alesci, Salvatore

AU - Chrousos, George P.

AU - Kino, Tomoshige

PY - 2004

Y1 - 2004

N2 - Glucocorticoids exert their extremely diverse effects on numerous biologic activities of humans via only one protein module, the glucocorticoid receptor (GR). The GR binds to the glucocorticoid response elements located in the promoter region of target genes and regulates their transcriptional activity. In addition, GR associates with other transcription factors through direct protein-protein interactions and mutually represses or stimulates each other's transcriptional activities. The latter activity of GR may be more important than the former one, granted that mice harboring a mutant GR, which is active in terms of protein-protein interactions but inactive in terms of transactivation via DNA, survive and procreate, in contrast to mice with a deletion of the entire GR gene that die immediately after birth. We recently found that GR physically interacts with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays a critical role in the metabolism of glucose, cholesterol, and xenobiotics, as wel as in the development of the central nervous system in fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors, such as the silencing mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear receptor compressors (NCoRs) via its C-terminal domain. Their mutual interaction may play an important role in gluconeogenesis, lipoprotein metabolism, and enzymatic clearance of clinically important compounds and bioactive chemicals, by regulating their rate-limiting enzymes and molecules, including the phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A, and several apolipoproteins. It appears that glucocorticoids exert their intermediary effects partly via physical interaction with COUP-TFII.

AB - Glucocorticoids exert their extremely diverse effects on numerous biologic activities of humans via only one protein module, the glucocorticoid receptor (GR). The GR binds to the glucocorticoid response elements located in the promoter region of target genes and regulates their transcriptional activity. In addition, GR associates with other transcription factors through direct protein-protein interactions and mutually represses or stimulates each other's transcriptional activities. The latter activity of GR may be more important than the former one, granted that mice harboring a mutant GR, which is active in terms of protein-protein interactions but inactive in terms of transactivation via DNA, survive and procreate, in contrast to mice with a deletion of the entire GR gene that die immediately after birth. We recently found that GR physically interacts with the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), which plays a critical role in the metabolism of glucose, cholesterol, and xenobiotics, as wel as in the development of the central nervous system in fetus. GR stimulates COUP-TFII-induced transactivation by attracting cofactors via its activation function-1, while COUP-TFII represses the GR-governed transcriptional activity by tethering corepressors, such as the silencing mediator for retinoid and thyroid hormone receptors (SMRT) and the nuclear receptor compressors (NCoRs) via its C-terminal domain. Their mutual interaction may play an important role in gluconeogenesis, lipoprotein metabolism, and enzymatic clearance of clinically important compounds and bioactive chemicals, by regulating their rate-limiting enzymes and molecules, including the phosphoenolpyruvate carboxykinase (PEPCK), the cytochrome P450 CYP3A and CYP7A, and several apolipoproteins. It appears that glucocorticoids exert their intermediary effects partly via physical interaction with COUP-TFII.

KW - Apolipoproteins

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KW - P450 CYP7A

KW - Phosphoenolpyruvate carboxykinase (PEPCK)

KW - Protein-protein interaction

KW - Xenobiotic metabolism

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U2 - 10.1196/annals.1321.006

DO - 10.1196/annals.1321.006

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JO - Annals of The Lyceum of Natural History of New York

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SN - 0890-6564

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