SREBP1A/1C/2 is retained in the endoplasmic reticulum by SCAP:cholesterol:INSIG

Stable Identifier
Reaction [omitted]
Cricetulus griseus
SVG |   | PPTX  | SBGN
SREBP1A/1C/2 is retained in the endoplasmic reticulum by SCAP:cholesterol:INSIG

SREBPs (SREBP1A/1C/2, SREBFs) bind SCAP in the endoplasmic reticulum membrane. Luminal loop 1 of SCAP binds cholesterol (Adams et al. 2003) which prevents SCAP from interacting with Sec24 in the CopII coat complex and allows SCAP to interact with INSIG instead (Sakai et al. 1997, Yang et al. 2002, Dobrosotskaya et al. 2003, Adams et al. 2004, Feramisco et al. 2005, Sun et al. 2005). These interactions retain SCAP:SREBP1A/1C/2 in the endoplasmic reticulum.

Literature References
PubMed ID Title Journal Year
12842885 Reconstitution of sterol-regulated endoplasmic reticulum-to-Golgi transport of SREBP-2 in insect cells by co-expression of mammalian SCAP and Insigs

Dobrosotskaya, IY, Goldstein, JL, Brown, MS, Rawson, RB

J Biol Chem 2003
12963821 Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles

Adams, CM, Goldstein, JL, Brown, MS

Proc Natl Acad Sci U S A 2003
15728349 Intramembrane aspartic acid in SCAP protein governs cholesterol-induced conformational change

Feramisco, JD, Radhakrishnan, A, Ikeda, Y, Reitz, J, Brown, MS, Goldstein, JL

Proc Natl Acad Sci U S A 2005
15452130 Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs

Adams, CM, Reitz, J, De Brabander, JK, Feramisco, JD, Li, L, Brown, MS, Goldstein, JL

J Biol Chem 2004
12202038 Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER

Yang, T, Espenshade, PJ, Wright, ME, Yabe, D, Gong, Y, Aebersold, R, Goldstein, JL, Brown, MS

Cell 2002
15899885 Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro

Sun, LP, Li, L, Goldstein, JL, Brown, MS

J Biol Chem 2005
9242699 Identification of complexes between the COOH-terminal domains of sterol regulatory element-binding proteins (SREBPs) and SREBP cleavage-activating protein

Sakai, J, Nohturfft, A, Cheng, D, Ho, YK, Brown, MS, Goldstein, JL

J Biol Chem 1997
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