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Functional Analysis of Nuclear Receptor FXR Controlling Metabolism of Cholesterol

OHNO, Masae

YAKUGAKU ZASSHI, 2008/03/01, Vol.128(3), pp.343-355 [Periódico revisado por pares]

Japan: The Pharmaceutical Society of Japan

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Título:
Functional Analysis of Nuclear Receptor FXR Controlling Metabolism of Cholesterol
Autor: OHNO, Masae
Assuntos: activation function-1 (AF-1) ; Animals ; Arteriosclerosis - etiology ; atherosclerosis ; Bile Acids and Salts - metabolism ; cholesterol ; Cholesterol - metabolism ; coactivator ; Diabetes Mellitus - etiology ; DNA-Binding Proteins - chemistry ; DNA-Binding Proteins - physiology ; Drug Design ; farnesoid X receptor (FXR) ; Humans ; Lipid Metabolism Disorders - etiology ; nuclear receptor ; Receptors, Cytoplasmic and Nuclear - chemistry ; Receptors, Cytoplasmic and Nuclear - physiology ; Transcription Factors - chemistry ; Transcription Factors - physiology
É parte de: YAKUGAKU ZASSHI, 2008/03/01, Vol.128(3), pp.343-355
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Descrição: Nuclear receptors function as ligand-inducible transcription factors that regulate various physiological functions such as development, reproduction, and metabolism. Dysregulation of the metabolism of cholesterol, triglyceride, and glucose leads to the metabolic syndrome including type 2 diabetes mellitus, obesity, dyslipidemia, and atherosclerosis. Studies of nuclear receptors promise to provide discoveries of therapeutic agents against the metabolic syndrome. Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is activated by bile acids. FXR regulates the metabolism of not only bile acid but also cholesterol, lipoprotein, triglyceride, and glucose, and is considered a potential therapeutic target for the metabolic syndrome because of these functions. Nuclear receptors have two regions for transactivation, a constitutive activation function (AF-1) and a ligand-dependent activation function (AF-2). AF-1 and AF-2 seem to require interactions with coactivators for the activation function and both work synergistically to give full transactivation of nuclear receptors. However, coactivators for AF-1 activity are poorly understood, whereas coactivators required for AF-2 activity have been well studied. To understand the molecular mechanism of AF-1 in FXR, we isolated proteins associated with AF-1 by GST pull-down assay using the N-terminal region of FXR and nuclear extracts from HeLa cells. This review focuses on the roles of FXR and our new findings regarding FXR-associated factors.
Editor: Japan: The Pharmaceutical Society of Japan
Idioma: Japonês;Inglês

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Functional Analysis of Nuclear Receptor FXR Controlling Metabolism of Cholesterol

OHNO, Masae

Japan: The Pharmaceutical Society of Japan

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