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Titolo:
NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells
Autore:
Lin, CJ; Martens, JWM; Miller, WL;
Indirizzi:
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Metab Res Unit, San Francisco, CA 94143 USA UnivCalif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 8, volume: 15, anno: 2001,
pagine: 1277 - 1293
SICI:
0888-8809(200108)15:8<1277:NSASAE>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
SIDE-CHAIN CLEAVAGE; NUCLEAR FACTOR-I; BOX-BINDING-PROTEINS; NEONATAL PIG TESTIS; BOVINE CYP11A GENE; CYTOCHROME B(5); MICROSOMAL CYTOCHROME-P-450; 17,20-LYASE ACTIVITY; BREAST-CANCER; STRUCTURAL CHARACTERIZATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
83
Recensione:
Indirizzi per estratti:
Indirizzo: Miller, WL Univ Calif San Francisco, Dept Pediat, Bldg MR 4,Room 209, San Francisco, CA 94143 USA Univ Calif San Francisco Bldg MR 4,Room 209 San Francisco CA USA 94143
Citazione:
C.J. Lin et al., "NF-1C, Sp1, and Sp3 are essential for transcription of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) in human adrenal NCI-H295A cells", MOL ENDOCR, 15(8), 2001, pp. 1277-1293

Abstract

Cytochrome P450c17 catalyzes steroid 17 alpha -hydroxylase and 17,20 lyaseactivities, which are required for the biosynthesis of cortisol and sex steroids. Human P450c17 is expressed in a cAMP-responsive, cell-specific, developmentally programmed fashion, but little is known about its transcriptional regulation. Expression of deletion mutants of up to 2,500 bp of human 5' -flanking DNA in human adrenal NCI-H295A cells indicated that most regulatory activity was confined to the first 227 bp. Deoxyribonuclease I footprinting of the proximal promoter identified the TATA box, an steroidogenic factor-1 site, and three previously uncharacterized sites at -107/85, at -178/-152, and at -220/-185. EMSAs and methylation interference assays suggested that the -107/-85 site and the -178/-152 site bind members of the NF-1 (nuclear factor-1) family of transcription factors. An NF-1 consensus sequence generated similar DNA/protein complexes, and antibodies against NF-1C2/CTF2 supershifted the complexes formed by the -107/-85 site, the -178/-152 site, and the NF-1 consensus site. Western blots of nuclear extracts from NCI-H295A cells probed with this NF-1 antiserum identified two NF-1 isoforms between 50 and 55 kDa. The presence of NF-1C2 (CTF2) and CTF5 in NCI-H295A cells was demonstrated by RT-PCR and sequencing. Mutation of both the -107/-85 and the -178/-152 NF-1 sites reduced basal transcription by half. Supershift assays showed that the ubiquitous proteins Sp1 and Sp3 both bind to the -227/-184 region, and that mutation of their binding sites reduced transcription by 75%. Mutation of the Sp1/Sp3 site plus the two NF-1 sites eliminated almost all detectable transcription. Thus, Sp1 and Sp3 binding to the-227/-184 site and NF-1C proteins binding to the -107/-85 and the -178/-152 sites are crucial for adrenal transcription of the human gene for P450c17.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 21:43:15