SREBP transcription factors: master regulators of lipid homeostasis

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of a range of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol and phospholipid synthesis. The three SREBP isoforms, SR...

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Veröffentlicht in:Biochimie Jg. 86; H. 11; S. 839 - 848
Hauptverfasser: Eberlé, Delphine, Hegarty, Bronwyn, Bossard, Pascale, Ferré, Pascal, Foufelle, Fabienne
Format: Journal Article
Sprache:Englisch
Veröffentlicht: France Elsevier Masson SAS 01.11.2004
Schlagworte:
Animals
CCAAT-Enhancer-Binding Proteins - biosynthesis
CCAAT-Enhancer-Binding Proteins - genetics
CCAAT-Enhancer-Binding Proteins - metabolism
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression Regulation
Homeostasis
Insulin
Lipid Metabolism
Lipids
Lipids - biosynthesis
Mice
Models, Biological
Protein Isoforms - biosynthesis
Protein Isoforms - genetics
Protein Isoforms - metabolism
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Sterol regulatory element binding proteins (SREBPs)
Transcription factors
Transcription Factors - biosynthesis
Transcription Factors - genetics
Transcription Factors - metabolism
aa
ACC
Transcription factors
SREBP
SRE
Lipids
bHLH-LZ
Sterol regulatory element binding proteins (SREBPs)
MAPK
Insulin
ER
ADD1
TG
STZ
AMPK
FAS
SCAP
FA
ISSN:0300-9084, 1638-6183
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Zusammenfassung:Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis by controlling the expression of a range of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol and phospholipid synthesis. The three SREBP isoforms, SREBP-1a, SREBP-1c and SREBP-2, have different roles in lipid synthesis. In vivo studies using transgenic and knockout mice suggest that SREBP-1c is involved in FA synthesis and insulin induced glucose metabolism (particularly in lipogenesis), whereas SREBP-2 is relatively specific to cholesterol synthesis. The SREBP-1a isoform seems to be implicated in both pathways. SREBP transcription factors are synthetized as inactive precursors bound to the endoplasmic reticulum (ER) membranes. Upon activation, the precursor undergoes a sequential two-step cleavage process to release the NH 2-terminal active domain in the nucleus (designated nSREBPs). SREBP processing is mainly controlled by cellular sterol content. When sterol levels decrease, the precursor is cleaved to activate cholesterogenic genes and maintain cholesterol homeostasis. This sterol-sensitive process appears to be a major point of regulation for the SREBP-1a and SREBP-2 isoforms but not for SREBP-1c. Moreover, the SREBP-1c isoform seems to be mainly regulated at the transcriptional level by insulin. The unique regulation and activation properties of each SREBP isoform facilitate the co-ordinate regulation of lipid metabolism; however, further studies are needed to understand the detailed regulation pathways that specifically regulate each SREBP isoform.
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ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2004.09.018