Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes

Prog Lipid Res. 2001 Nov;40(6):439-52. doi: 10.1016/s0163-7827(01)00010-8.

Abstract

Roles of sterol regulatory element-binding proteins (SREBPs) have been established as lipid synthetic transcription factors especially for cholesterol and fatty acid synthesis. SREBPs have unique characteristics. Firstly, they are membrane-bound proteins and the N-terminal active portions enter nucleus to activate their target genes after proteolytic cleavage, which requires sterol-sensing molecule, SREBP-activating protein (SCAP) and is crucial for sterol-regulation. Secondly, they bind and activate sterol-regulatory (SREs) containing promoters as well as some E-boxes, which makes SREBPs eligible to regulate a wide range of lipid genes. Finally, three isoforms, SREBP-1a-1c, and have different roles in lipid synthesis. In vivo studies using transgenic and knockout mice suggest that SREBP-1 seems to be involved in energy metabolism including fatty acid and glucose/insulin metabolism, whereas SREBP-2 is specific to cholesterol synthesis. Future studies will be focused on understanding molecular mechanisms sensing cellular sterol and energy states where SREBPs are deeply involved.

Publication types

  • Review

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Membrane / metabolism
  • Cholesterol / biosynthesis
  • Cholesterol / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • E-Box Elements
  • Fatty Acids / metabolism
  • Fungal Proteins*
  • GATA Transcription Factors
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glucose / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Insulin / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Lipids / biosynthesis*
  • Liver / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors*
  • Transcription, Genetic*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Fatty Acids
  • Fungal Proteins
  • GATA Transcription Factors
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Lipids
  • Membrane Proteins
  • SREBF1 protein, human
  • SREBP cleavage-activating protein
  • Sre protein, Neurospora crassa
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Cholesterol
  • Glucose