PUBLICATION
Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins
- Authors
- Yabe, D., Brown, M.S., and Goldstein, J.L.
- ID
- ZDB-PUB-040202-5
- Date
- 2002
- Source
- Proceedings of the National Academy of Sciences of the United States of America 99(20): 12753-12758 (Other)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Cricetinae
- Carrier Proteins/chemistry*
- Carrier Proteins/physiology*
- Protein Binding
- Sequence Homology, Amino Acid
- DNA, Complementary/metabolism
- Golgi Apparatus/metabolism
- Plasmids/metabolism
- Molecular Sequence Data
- Cells, Cultured
- Mice
- Membrane Proteins/chemistry*
- Membrane Proteins/metabolism*
- Membrane Proteins/physiology*
- Precipitin Tests
- Cholesterol/metabolism
- Sterol Regulatory Element Binding Protein 1
- Immunoblotting
- Promoter Regions, Genetic
- Transfection
- DNA-Binding Proteins/metabolism*
- Endoplasmic Reticulum/metabolism*
- Intracellular Signaling Peptides and Proteins*
- CCAAT-Enhancer-Binding Proteins/metabolism*
- Mutation
- Time Factors
- Animals
- Dose-Response Relationship, Drug
- Humans
- Proteins/metabolism*
- Proteins/physiology*
- Transcription Factors*
- Blotting, Northern
- CHO Cells
- PubMed
- 12242332 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Yabe, D., Brown, M.S., and Goldstein, J.L. (2002) Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proceedings of the National Academy of Sciences of the United States of America. 99(20):12753-12758.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping