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Titolo:
C T POLYMORPHISM IN THE 5' UNTRANSLATED REGION OF THE APOLIPOPROTEIN(A) GENE INTRODUCES AN UPSTREAM ATG AND REDUCES IN-VITRO TRANSLATION/
Autore:
ZYSOW BR; LINDAHL GE; WADE DP; KNIGHT BL; LAWN RM;
Indirizzi:
STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR STANFORD CA 94305 STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR STANFORD CA 94305 HAMMERSMITH HOSP,MRC,LIPOPROT TEAM LONDON W12 0HS ENGLAND
Titolo Testata:
Arteriosclerosis, thrombosis, and vascular biology
fascicolo: 1, volume: 15, anno: 1995,
pagine: 58 - 64
SICI:
1079-5642(1995)15:1<58:CTPIT5>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-GLOBIN GENE; PLASMA LIPOPROTEIN(A) CONCENTRATION; LP(A) GLYCOPROTEIN PHENOTYPES; INITIATION CODON MUTATION; MESSENGER-RNA; SIZE HETEROGENEITY; THALASSEMIA; SEQUENCE; QUANTITATION; PLASMINOGEN;
Keywords:
APOLIPOPROTEIN; ATG INITIATION CODON; LIPOPROTEIN(A); POLYMORPHISM; ATHEROSCLEROSIS; TRANSLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
B.R. Zysow et al., "C T POLYMORPHISM IN THE 5' UNTRANSLATED REGION OF THE APOLIPOPROTEIN(A) GENE INTRODUCES AN UPSTREAM ATG AND REDUCES IN-VITRO TRANSLATION/", Arteriosclerosis, thrombosis, and vascular biology, 15(1), 1995, pp. 58-64

Abstract

Elevated plasma levels of lipoproteinz(a) [Lp(a)] are a significant independent risk factor for arteriosclerosis. Interindividual levels ofLp(a) vary nearly 1000-fold and are mainly due to inheritance that islinked to the locus of the apolipoprotein(a) [apo(a)] gene. A search was made for sequence variants in the 5' flanking region of the apo(a)gene that affect its expression. A C to T transition at position +93 from the transcription start site was found with a frequency of 14% inthe study population. In transient transfection assays in HepG2 cells, luciferase reporter gene constructs with a T at this position were associated with a 58% reduction in luciferase activity compared with the more common allele. This single base variant had no significant effect on the binding of nuclear regulatory proteins; however, it introduced an additional upstream ATG initiation codon with its own in-frame stop codon. Furthermore, equivalent levels of mRNA were produced in HepG2 cells transfected with reporter gene constructs containing either aT or a C at position +93. In vitro translation experiments using transcripts derived from either variant apo(a) promoter revealed a 60% reduction in translation associated with the T allele. Hence, the additional ATG created by the T at position +93 in the 5' flanking region of the apo(a) gene impairs the efficiency of translation from the bona fide ATG initiation codon.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 13:02:27