SREBP-1 Mediates Activation of the Low Density Lipoprotein Receptor Promoter by Insulin and Insulin-like Growth Factor-I

• DOI: 10.1074/jbc.271.12.7128
• Publication Date: 2002-07-26T14:52:05Z
• Authors: Rüdiger Streicher; Jörg Kotzka; Dirk Müller-Wieland; Gerhard Siemeister; Martina Munck; Haluk Avci; Wilhelm Krone
• Keywords: Insulin receptor substrate; GRB10

Transcription of the low density lipoprotein (LDL) receptor gene is regulated by intracellular cholesterol concentration, hormones, and growth factors. We studied mechanisms which insulin estradiol stimulate promoter activity LDL gene. Hormonal effects were analyzed in HepG2 cells after transient transfection with promotor reporter constructs. Successive 5' deletions fragment from -537 to +88 revealed sterol regulatory element 1 (SRE-1) between -65 -56 as an insulin- estradiol-sensitive cis-element. If SRE-1 point mutated at position -59 (C G), abolishes binding SRE proteins (SREBP-1 SREBP-2), no or stimulatory effect on expression was observed, indicating a role this mechanism. The concentration 125-kDa membrane-integrated SREBP-1 precursor protein repressed not altered hormone treatment. Concentrations mRNA are reduced significantly high stable antisense cDNA (SREBP1(-) cells). Transfection SREBP1(-) construct phLDL4 (-105 +88) reduces induction insulin-like factor-I 35 17%, respectively, compared cells. remains unchanged, inductions pravastatin enlarged. conclude that different converge SRE-1, but selectively involved signal transduction pathway leading activation.