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Titolo:
The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATPbinding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux
Autore:
Porsch-Ozcurumez, M; Langmann, T; Heimerl, S; Borsukova, H; Kaminski, WE; Drobnik, W; Honer, C; Schumacher, C; Schmitz, G;
Indirizzi:
Univ Regensburg, Inst Clin Chem, D-8400 Regensburg, Germany Univ Regensburg Regensburg Germany D-8400 em, D-8400 Regensburg, Germany Novartis Inst Biomed Res, Summit, NJ 07901 USA Novartis Inst Biomed Res Summit NJ USA 07901 ed Res, Summit, NJ 07901 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 15, volume: 276, anno: 2001,
pagine: 12427 - 12433
SICI:
0021-9258(20010413)276:15<12427:TZFP2(>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
TANGIER-DISEASE PATIENTS; DENSITY-LIPOPROTEIN; CHOLESTEROL EFFLUX; MOLECULAR-CLONING; PLASMA-MEMBRANE; APOA-I; PROMOTER; DOMAIN; COREPRESSOR; MACROPHAGES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Schmitz, G Univ Klinikum Regensburg, Inst Klin Chem & Blutbank, Franz Josef Strauss Allee 11, D-93042 Regensburg, Germany Univ Klinikum Regensburg Franz Josef Strauss Allee 11 Regensburg Germany D-93042
Citazione:
M. Porsch-Ozcurumez et al., "The zinc finger protein 202 (ZNF202) is a transcriptional repressor of ATPbinding cassette transporter A1 (ABCA1) and ABCG1 gene expression and a modulator of cellular lipid efflux", J BIOL CHEM, 276(15), 2001, pp. 12427-12433

Abstract

The zinc finger gene 202 (ZNF202) located within a hypoalphalipoproteinemia susceptibility locus on chromosome 11q23 is a transcriptional repressor of various genes involved in lipid metabolism. To provide further evidence for a functional linkage between ZNF202 and hypoalphalipoproteinemia, we investigated the effect of ZNF202 expression on ATP binding cassette transporter A1 (ABCA1) and ABCG1, ABCA1 is a key regulator of the plasma high density lipoprotein pool size, whereas ABCG1 is another mediator of cellular cholesterol and phospholipid efflux in human macrophage. We demonstrate here that the full-length ZNF202m1 isoform binds to GnT repeats within the promoters of ABCA1 (-229/ -210) and ABCG1 (-572/-552), ZNF202m1 expression in HepG2 cells dose-dependently repressed the promotor activities of ABCA1 and ABCG1, This transcriptional effect required the presence of the SCAN domain inZNF202 and the functional integrity of a TATA box at position -24 of ABCA1, whereas the presence of GnT binding motifs was nonessential. The state ofZNF202 SCAN domain oligomerization affected the ability of the adjacent ZNF202 Kruppel-associated box domain to recruit the transcriptional corepressor KAP1, Overexpression of ZNF202m1 in RAW264.7 macrophages prevented the induction of ABCA1 gene expression by 20(S)OH-cholesterol and 9-cis-retinoicacid, further substantiating the interference of ZNF202 in critical elements of transcriptional activation, Finally, HDL and apoAI-mediated lipid efflux was significantly reduced in RAW264.7 cells stably expressing ZNF202m1,In conclusion, we have identified ABCA1 and ABCG1 as target genes for ZNF202-mediated repression and thus, provide evidence for a functional linkage between ZNF202 and hypoalphalipoproteinemia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 03:27:48