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Cited by 478

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins

Yabe, Daisuke, Brown, Michael S., Goldstein, Joseph L.·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.162488899
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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.

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  • Under sufficient cellular sterols, SREBPs are retained in the ER through formation of a tripartite complex with SCAP and INSIG1/2.

    “Under conditions of sufficient cellular sterols, SREBPs are retained in the ER through formation of a tripartite complex with the sterol-sensing SREBP cleavage-activating protein (SCAP)7,8, and the ER anchor proteins insulin-induced genes 1 and 2 (INSIG1 and 2)9,10.”

    From Haploid genetic screens identify SPRING/C12ORF49 as a determinant of SREBP signaling and cholesterol metabolism (2020) · cites this paper as [10]

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Citations

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Research works printed but not linked: 23

  1. M S Brown, J L Goldstein Proc Natl Acad Sci USA 96, 11041–11048 (1999). · DOI · Paper page
  2. P A Edwards, D Tabor, H R Kast, A Venkateswaran Biochim Biophys Acta 1529, 103–113 (2000). · DOI
  3. J L Goldstein, R B Rawson, M S Brown Arch Biochem Biophys 397, 139–148 (2002). · DOI · Paper page
  4. Brown A. J. Sun L. Feramisco J. D. Brown M. S. & Goldstein J. L. (2002) Mol. Cell in press.
  5. V C Hannah, J Ou, A Luong, J L Goldstein, M S Brown J Biol Chem 276, 4365–4372 (2001). · DOI · Paper page
  6. Yang T. Espenshade P. J. Wright M. E. Yabe D. Gong Y. Aebersold R. Goldstein J. L. & Brown M. S. (2002) Cell in press.
  7. T Yang, J L Goldstein, M S Brown J Biol Chem 275, 29881–29886 (2000). · DOI
  8. X Hua, J Sakai, M S Brown, J L Goldstein J Biol Chem 271, 10379–10384 (1996). · DOI
  9. J Sakai, A Nohturfft, D Cheng, Y K Ho, M S Brown, J L Goldstein J Biol Chem 272, 20213–20221 (1997). · DOI · Paper page
  10. A Nohturfft, D Yabe, J L Goldstein, M S Brown, P J Espenshade Cell 102, 315–323 (2000). · DOI
  11. J E Metherall, J L Goldstein, K L Luskey, M S Brown J Biol Chem 264, 15634–15641 (1989). · DOI
  12. R B Rawson, D Cheng, M S Brown, J L Goldstein J Biol Chem 273, 28261–28269 (1998). · DOI
  13. M T Hasan, T Y Chang Somatic Cell Mol Genet 20, 481–491 (1994). · DOI
  14. R B Rawson, R DeBose-Boyd, J L Goldstein, M S Brown J Biol Chem 274, 28549–28556 (1999). · DOI · Paper page
  15. J Pai, O Guryev, M S Brown, J L Goldstein J Biol Chem 273, 26138–26148 (1998). · DOI
  16. I Shimomura, H Shimano, J D Horton, J L Goldstein, M S Brown J Clin Invest 99, 838–845 (1997). · DOI
  17. A Nohturfft, R A DeBose-Boyd, S Scheek, J L Goldstein, M S Brown Proc Natl Acad Sci USA 96, 11235–11240 (1999). · DOI · Paper page
  18. A Luong Ph.D. dissertation (University of Texas Southwestern Medical Center, Dallas, 2000).
  19. Z Sheng, H Otani, M S Brown, J L Goldstein Proc Natl Acad Sci USA 92, 935–938 (1995). · DOI · Paper page
  20. J J Repa, G Liang, J Ou, Y Bashmakov, J-M A Lobaccaro, I Shimomura, B Shan, M S Brown, J L Goldstein, D J Mangelsdorf Genes Dev 14, 2819–2830 (2000). · DOI
  21. R A DeBose-Boyd, J Ou, J L Goldstein, M S Brown Proc Natl Acad Sci USA 98, 1477–1482 (2001). · DOI · Paper page
  22. J Kyte, R F Doolittle J Mol Biol 157, 105–132 (1982). · DOI
  23. W R Pearson, T Wood, Z Zhang, W Miller Genomics 46, 24–36 (1997). · DOI

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Metadata

Authors
Yabe, D., Brown, M. S., & Goldstein, J. L.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2002-09-19
Volume
99
Issue
20
Pages
12753-12758
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.162488899
Cited by
478
References
1
Language
en

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