Sterol regulatory element binding proteins (SREBPs): controllers of lipid synthesis and cellular uptake.
Mammalian cells use an exquisitely sensitive mechanism to control the amount of cholesterol and fatty acids in their membranes. This process relies on a feedback system that adjusts the rates of transcription of genes encoding the low density lipoprotein receptor and multiple enzymes in the cholesterol and fatty acid biosynthetic pathways. When cellular cholesterol levels are depleted, these genes are all transcribed in abundant amounts, and their transcription is repressed when sterols build up within the cell. Until recently, the mechanism of this regulation was elusive. How do cells sense the level of a membrane-embedded lipid such as cholesterol and how is this information transmitted to the nucleus where gene transcription is regulated? Answers are now beginning to emerge from the study of a newly discovered family of transcription-regulating proteins called sterol regulatory element binding proteins.
Brown
M S
MS
Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Goldstein
J L
JL
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005227:Fatty Acids / Q000096:biosynthesis*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D009687:Nuclear Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002784:Cholesterol