TY - JOUR
T1 - Regulation of sterol synthesis in eukaryotes
AU - Espenshade, Peter J.
AU - Hughes, Adam L.
PY - 2007/12/1
Y1 - 2007/12/1
N2 - Cholesterol is an essential component of mammalian cell membranes and is required for proper membrane permeability, fluidity, organelle identity, and protein function. Cells maintain sterol homeostasis by multiple feedback controls that act through transcriptional and posttranscriptional mechanisms. The membrane-bound transcription factor sterol regulatory element binding protein (SREBP) is the principal regulator of both sterol synthesis and uptake. In mammalian cells, the ER membrane protein Insig has emerged as a key component of homeostatic regulation by controlling both the activity of SREBP and the sterol-dependent degradation of the biosynthetic enzyme HMG-CoA reductase. In this review, we focus on recent advances in our understanding of the molecular mechanisms of the regulation of sterol synthesis. A comparative analysis of SREBP and HMG-CoA reductase regulation in mammals, yeast, and flies points toward an equilibrium model for how lipid signals regulate the activity of sterol-sensing proteins and their downstream effectors.
AB - Cholesterol is an essential component of mammalian cell membranes and is required for proper membrane permeability, fluidity, organelle identity, and protein function. Cells maintain sterol homeostasis by multiple feedback controls that act through transcriptional and posttranscriptional mechanisms. The membrane-bound transcription factor sterol regulatory element binding protein (SREBP) is the principal regulator of both sterol synthesis and uptake. In mammalian cells, the ER membrane protein Insig has emerged as a key component of homeostatic regulation by controlling both the activity of SREBP and the sterol-dependent degradation of the biosynthetic enzyme HMG-CoA reductase. In this review, we focus on recent advances in our understanding of the molecular mechanisms of the regulation of sterol synthesis. A comparative analysis of SREBP and HMG-CoA reductase regulation in mammals, yeast, and flies points toward an equilibrium model for how lipid signals regulate the activity of sterol-sensing proteins and their downstream effectors.
KW - Cholesterol synthesis
KW - Endoplasmic reticulum
KW - HMG-CoA reductase
KW - Insig
KW - SREBP
KW - Scap
KW - Yeast
UR - http://www.scopus.com/inward/record.url?scp=39849102805&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39849102805&partnerID=8YFLogxK
U2 - 10.1146/annurev.genet.41.110306.130315
DO - 10.1146/annurev.genet.41.110306.130315
M3 - Review article
C2 - 17666007
AN - SCOPUS:39849102805
SN - 0066-4197
VL - 41
SP - 401
EP - 427
JO - Annual review of genetics
JF - Annual review of genetics
ER -