TY - JOUR
T1 - Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi
T2 - Oxysterols block transport by binding to Insig
AU - Radhakrishnan, Arun
AU - Ikeda, Yukio
AU - Hyock, Joo Kwon
AU - Brown, Michael S.
AU - Goldstein, Joseph L.
PY - 2007/4/17
Y1 - 2007/4/17
N2 - Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.
AB - Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.
KW - COPII vesicles
KW - Cholesterol homeostasis
KW - Scap
KW - Sterol regulatory element-binding protein pathway
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U2 - 10.1073/pnas.0700899104
DO - 10.1073/pnas.0700899104
M3 - Article
C2 - 17428920
AN - SCOPUS:34249848111
SN - 0027-8424
VL - 104
SP - 6511
EP - 6518
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -