The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins
Open accessAbstract
Two classes of sterols, cholesterol and oxysterols, block export of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi by preventing the binding of COPII-coated proteins to a hexapeptide sorting signal (MELADL) in Scap, the SREBP-escort protein. Here, we show that anti-MELADL blocks COPII binding in vitro , and microinjection of Fab anti-MELADL blocks Scap·SREBP movement in cells. Cholesterol and oxysterols block COPII binding to MELADL by binding to different intracellular receptors, cholesterol to Scap and oxysterols to Insig. Cysteine labeling shows that both binding events produce a conformational change near the MELADL sequence, abrogating COPII binding but not anti-MELADL binding. Mutagenesis experiments raise the possibility that the distance of MELADL from the ER membrane is crucial for COPII binding, and we speculate that sterols and Insig block SREBP transport by altering the location of MELADL with respect to the membrane, rendering it inaccessible to COPII proteins.
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Self-citationCellular Cholesterol Efflux Mediated by Cyclodextrins
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Endoplasmic Reticulum Stress Sensing in the Unfolded Protein Response
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Regulation of Sterol Synthesis in Eukaryotes
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Radhakrishnan, A., Ikeda, Y., Kwon, H. J., Brown, M. S., & Goldstein, J. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700899104 · Cited by 556
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Metadata
- Authors
- Sun, L.-P., Seemann, J., Goldstein, J. L., & Brown, M. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-04-17
- Volume
- 104
- Issue
- 16
- Pages
- 6519-6526
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2089086088
- Cited by
- 309
- References
- 35
- FWCI
- 22.93
- Type
- journal article
- Language
- en
- Open access
- green
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- Sun, L.-P., Seemann, J., Goldstein, J. L., & Brown, M. S. (2007). Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0700907104
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