Related Experiment Video
Updated: Aug 8, 2026

Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Sterol regulatory element-binding protein-2 negatively regulates low density lipoprotein receptor-related protein
V Llorente-Cortés1, P Costales, J Bernués
1Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, 08025, Spain.
Abstract:
Low density lipoprotein receptor-related protein (LRP1) binds aggregated LDL (agLDL) leading to a high intracellular cholesteryl ester (CE) accumulation. AgLDL up-regulates LRP1 expression concomitantly with an LDL receptor (LDLR) and sterol regulatory element binding protein (SREBP-2) down-regulation. The objectives were to investigate whether SREBP-2 regulates LRP1 transcription and determine the molecular mechanisms involved in the process. Down-regulation of active SREBP-2 by nLDL and agLDL led to LDLR down-regulation and LRP1 up-regulation. Enforced expression of an active form of SREBP-2 (SREBP-2-NT, amino acid residues 1-468) decreased LRP1 expression and LRP1 promoter (WT-LRP1) luciferase activity in a dose-dependent manner. LDL did not exert any significant effect on LRP1 promoter activity when a putative sterol regulatory element (SRE) (5-GTGGGGTGA-3'; +225 to +233) was mutated (SRE-MT-LRP1). SREBP-2 overexpression exerted stronger down-regulatory effects on WT-LRP1 than on SRE-MT-LRP1 promoter activity both in control, nLDL- and agLDL-exposed HeLa cells. Gel mobility shift assays showed that recombinant SREBP-2-NT protein (1-468) binds to a double-stranded LRP1 DNA fragment (215 to 245) containing a wild-type (wt) SRE sequence but not to a mutated SRE (mt) sequence (5-GAATTCGA-3'). Our results demonstrate that LDL stimulates LRP1 transcription and decreases SREBP-2 active form which negatively regulates LRP1 transcription. SRE sequence (+225 to +233) plays a pivotal role for the down-regulatory effect of SREBP-2 on LRP1 promoter activity.
Related Concept Videos
Master Transcription Regulators
Co-activators and Co-repressors
Co-activators and Co-repressors
RNA Polymerase II Accessory Proteins
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Regulation of Nuclear Protein Sorting
