The apolipoprotein(a) promoter contains a retinoid response element

Biochemical and Biophysical Research Communications
R RamharackM A Spahr

Abstract

Retinoids were previously shown to lower apolipoprotein(a) [apo(a)] mRNA levels, suggesting that the apo(a) promoter contains a retinoid response element (RRE). Scanning the apo(a) promoter for sequences related to the consensus RRE half-site (5'-PuG(G/T)TCA-3') uncovered four sites that could potentially function as RREs at -2915, -1875, -1036, and -407. The activity of these sites was assessed by their ability to compete with a very strong consensus DR5 RRE for binding to retinoic acid receptor (RARalpha) and retinoid X receptor (RXRalpha) heterodimers using electrophoretic mobility-shift assays. Only the -1036 site (5'-TGACCTTGTGATCC-'3) was an effective competitor of the DR5 RRE; therefore, it was designated as apo(a) RRE. Apo(a) RRE competed with DR5 RRE for RARalpha/RXRalpha binding with 1/10 the affinity of DR5 RRE, while a scrambled apo(a) RRE was inactive. These results suggested that apo(a) RRE is a potential candidate for mediating the effect retinoids have on apo(a) mRNA expression.

References

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Citations

Jun 28, 2006·Biological Chemistry·Ying ZhangVimla Band
Jun 28, 2006·Biological Chemistry·Musheng ZengVimla Band
Aug 4, 1999·Current Opinion in Lipidology·H H Hobbs, A L White
Mar 14, 2002·Biochemical and Biophysical Research Communications·Vikas HandaMehboob ul-Hussain

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