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Titolo:
Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter
Autore:
Yoshikawa, T; Shimano, H; Amemiya-Kudo, M; Yahagi, N; Hasty, AH; Matsuzaka, T; Okazaki, K; Tamura, Y; Iizuka, Y; Ohashi, K; Osuga, JI; Harada, K; Gotoda, T; Kimura, S; Ishibashi, S; Yamada, N;
Indirizzi:
Univ Tsukuba, Inst Clin Med, Dept Internal Med, Tsukuba, Ibaraki 3058575, Japan Univ Tsukuba Tsukuba Ibaraki Japan 3058575 sukuba, Ibaraki 3058575, Japan Univ Tokyo, Dept Metab Dis, Bunkyo Ku, Tokyo 1138655, Japan Univ Tokyo Tokyo Japan 1138655 etab Dis, Bunkyo Ku, Tokyo 1138655, Japan
Titolo Testata:
MOLECULAR AND CELLULAR BIOLOGY
fascicolo: 9, volume: 21, anno: 2001,
pagine: 2991 - 3000
SICI:
0270-7306(200105)21:9<2991:IOLXRX>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLYUNSATURATED FATTY-ACIDS; LEUCINE ZIPPER PROTEIN; SREBP-1C MESSENGER-RNA; TRANSGENIC MICE; TRANSCRIPTION FACTOR; LXR-ALPHA; CHOLESTEROL-SYNTHESIS; ADIPOSE-TISSUE; CULTURED-CELLS; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Shimano, H Univ Tsukuba, Inst Clin Med, Dept Internal Med, 1-1-1 Tennodai,Tsukuba, Ibaraki 3058575, Japan Univ Tsukuba 1-1-1 Tennodai Tsukuba Ibaraki Japan 3058575 Japan
Citazione:
T. Yoshikawa et al., "Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter", MOL CELL B, 21(9), 2001, pp. 2991-3000

Abstract

In an attempt to identify transcription factors which activate sterol-regulatory element-binding protein Ic (SREBP-1c) transcription, we screened an expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse SREBP-1 gene promoter. We cloned and identified the oxysterol receptors liver X receptor (LXR alpha) and LXR beta as strong activators of the mouse SREBP-1c promoter. In the transfection studies, expression of either LXR alpha or -beta activated the SREBP-1c promoter-luciferase gene in a dose-dependent manner. Deletion and mutation studies, as well as gel mobility shift assays, located an LXR response element complex consisting of two new LXR-binding motifs which showed high similarity to an LXR response element recently found in the ABC1 gene promoter, a reverse cholesterol transporter. Addition of an LXR ligand, 22(R)-hydroxycholesterol, increased the promoter activity. Coexpression of retinoid X receptor (RXR), a heterodimeric partner, and its ligand 9-cis-retinoic acid also synergistically activated the SREBP-1c promoter. In HepG2 cells, SREBP-1c mRNA and precursor protein levels were induced by treatment with 22(R)-hydroxycholesterol and 9-cis-retinoic acid, confirming that endogenous LXR-RXR activation can induce endogenous SREBP-1c expression. The activationof SREBP-1c by LXR is associated with a slight increase in nuclear SREBP-1c, resulting in activation of the gene for fatty acid synthase, one of its downstream genes, as measured by the luciferase assay. These data demonstrate that LXR-RXR can modify the expression of genes for lipogenic enzymes byregulating SREBP-1c expression, providing a novel link between fatty acid and cholesterol metabolism.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:19:59