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Titolo:
Acceleration of thrombomodulin gene transcription by retinoic acid - Retinoic acid receptors and Sp1 regulate the promoter activity through interactions with two different sequences in the 5 '-flanking region of human gene
Autore:
Horie, S; Ishii, H; Matsumoto, F; Kusano, M; Kizaki, K; Matsuda, J; Kazama, M;
Indirizzi:
Teikyo Univ, Fac Pharmaceut Sci, Dept Clin Biochem, Kanagawa 1990195, Japan Teikyo Univ Kanagawa Japan 1990195 Clin Biochem, Kanagawa 1990195, Japan Showa Coll Pharmaceut Sci, Dept Publ Hlth, Tokyo 1948543, Japan Showa CollPharmaceut Sci Tokyo Japan 1948543 Hlth, Tokyo 1948543, Japan
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 4, volume: 276, anno: 2001,
pagine: 2440 - 2450
SICI:
0021-9258(20010126)276:4<2440:AOTGTB>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN ENDOTHELIAL-CELLS; TUMOR-NECROSIS-FACTOR; THROMBIN-CATALYZED ACTIVATION; DEPENDENT PROTEIN-KINASE; X-RECEPTOR; THYROID-HORMONE; TISSUE-FACTOR; NUCLEAR RECEPTORS; ANTICOAGULANT ACTIVITY; ESTROGEN-RECEPTOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Horie, S Teikyo Univ, Fac Pharmaceut Sci, Dept Clin Biochem, 1091-1 Suarashi, Kanagawa 1990195, Japan Teikyo Univ 1091-1 Suarashi Kanagawa Japan 1990195 990195, Japan
Citazione:
S. Horie et al., "Acceleration of thrombomodulin gene transcription by retinoic acid - Retinoic acid receptors and Sp1 regulate the promoter activity through interactions with two different sequences in the 5 '-flanking region of human gene", J BIOL CHEM, 276(4), 2001, pp. 2440-2450

Abstract

The interactions between retinoic acid- (RA)-dependent transcriptional regulatory sequences of the 5'-untranslated region of the thrombomodulin gene and nuclear RA-responsive proteins were studied using human pancreas BxPC-3cells. Deletion mutants of pTM-CAT plasmid revealed the presence of distaland proximal RA-responsive regions containing direct repeat with 4 spaces (DR4) and three of four Spl sites, respectively. Cotransfection of a pTM-CAT plasmid with expression plasmids of RA receptors (RAR alpha, RAR beta, and RAR gamma) augmented the promoter activity under the condition of lower retinoid X receptor-alpha (RXR alpha) expression, whereas the activity was greatly diminished when RXR alpha was highly expressed. An electrophoretic mobility shift assay with cDNA containing the DR4 indicated that heterodimers of RAR and RXR alpha interacted with the DR4 site, although the interaction gradually disappeared with the increase in the ratio of RXR alpha /RAR. On the other hand, Spl protein interacted especially with the tandem Spl site corresponding to the first and second Spl sequences of the four Spl sites in the proximal RA-responsive region. The binding of Spl to Spl sites wasindependent of RAR-RXR heterodimer but increased with the increase in Spl concentration in the presence of unknown factor(s) of reticulocyte lysate, Upon treatment of the cells with RA, time-dependent increases in the ratio of RAR beta to RXR alpha and the phosphorylated form of Spl were observed. We concluded that two genomic DNA regions, the DR4 site (-1531 to -1516) and the first and second Spl-binding sites (-145 to -121), were involved in the RA-dependent augmentation of thrombomodulin gene expression through increased interactions of the two regions with heterodimer of RAR-RXR alpha andnuclear Spl, respectively.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 20:35:55