Structure of the low-density lipoprotein receptor-related protein (LRP) promoter

The low-density Lipoprotein receptor-related protein (LRP) is a 4544-amino-acid membrane protein which closely resembles the LDL receptor in its arrangement of cysteine-rich motifs. Binding studies have suggested that one function of the molecule is as a receptor for ligands containing apolipoprotein E. We present here the sequence and structure of the promoter region of the LRP. These data show that the LRP contains no sterol regulatory element, and is not down-regulated by sterols like the LDL receptor. This lends further support to the identity of the LRP as a chylomicron remnant receptor.     

The E-box like sterol regulatory element mediates the suppression of human Delta-6 desaturase gene by highly unsaturated fatty acids

Delta-6 Desaturase (D6D) catalyzes the first step of the synthesis of highly unsaturated fatty acids (HUFA) that play pivotal roles in many biological functions. The D6D expression is under feedback regulation by dietary HUFA. We co-transfected D6D promoter-reporter constructs to HepG2 cells with an expression vector of nuclear form sterol regulatory element binding protein-1c (SREBP-1c). A 90-bp region of the D6D promoter was required for the activation by SREBP-1c as well as for the suppression of the promoter activity by HUFA. The region contained two candidates of sterol regulatory element (SRE). Mutation analysis identified E-box like SRE (SRE-2) as essential for both SREBP-1c activation and HUFA suppression. SRE-2 has a core sequence of CAGCAG, and is also conserved in stearoyl CoA desatruases. Because HUFA are primarily incorporated into phospholipids (PL), our results suggest that the primary role of SREBP-1c in liver is the regulation of fatty acid supply for PL rather than for triglycerides.