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PMID:12242332
| Citation |
Yabe, D, Brown, MS and Goldstein, JL (2002) Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 99:12753-8 |
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| Abstract |
This paper describes insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. By blocking this movement, insig-2, like the previously described insig-1, prevents the proteolytic processing of SREBPs by Golgi enzymes, thereby blocking cholesterol synthesis. The sequences of human insig-1 and -2 are 59% identical. Both proteins are predicted to contain six transmembrane helices. The proteins differ functionally in two respects: (i) production of insig-1, but not insig-2, in cultured mammalian cells requires nuclear SREBPs; and (ii) at high levels of expression, insig-1, but not insig-2, can block SCAP movement in the absence of exogenous sterols. The combined actions of insig-1 and -2 permit feedback regulation of cholesterol synthesis over a wide range of sterol concentrations. |
| Links |
PubMed PMC130532 Online version:10.1073/pnas.162488899 |
| Keywords |
Amino Acid Sequence; Animals; Blotting, Northern; CCAAT-Enhancer-Binding Proteins/metabolism; CHO Cells; Carrier Proteins/chemistry; Carrier Proteins/physiology; Cells, Cultured; Cholesterol/metabolism; Cricetinae; DNA, Complementary/metabolism; DNA-Binding Proteins/metabolism; Dose-Response Relationship, Drug; Endoplasmic Reticulum/metabolism; Golgi Apparatus/metabolism; Humans; Immunoblotting; Intracellular Signaling Peptides and Proteins; Membrane Proteins/chemistry; Membrane Proteins/metabolism; Membrane Proteins/physiology; Mice; Molecular Sequence Data; Mutation; Plasmids/metabolism; Precipitin Tests; Promoter Regions, Genetic; Protein Binding; Proteins/metabolism; Proteins/physiology; Sequence Homology, Amino Acid; Sterol Regulatory Element Binding Protein 1; Time Factors; Transcription Factors; Transfection |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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