TY - JOUR
T1 - Transport-dependent proteolysis of SREBP
T2 - Relocation of Site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi
AU - DeBose-Boyd, Russell A.
AU - Brown, Michael S.
AU - Li, Wei Ping
AU - Nohturfft, Axel
AU - Goldstein, Joseph L.
AU - Espenshade, Peter J.
N1 - Funding Information:
We thank Tammy Dinh for excellent technical assistance and Lisa Beatty and Anna Fuller for invaluable help with tissue culture. This work was supported by grants from the National Institutes of Health (NIH) (HL-20948) and the Perot Family Foundation. R. A. D.-B. is the recipient of a postdoctoral fellowship for the Jane Coffin Childs Memorial Fund. P. J. E. is the recipient of an NIH Research Science Fellowship Grant (HL-09993).
PY - 1999/12/23
Y1 - 1999/12/23
N2 - Cholesterol homeostasis in animal cells is achieved by regulated cleavage of membrane-bound transcription factors, designated SREBPs. Proteolytic release of the active domains of SREBPs from membranes requires a sterol-sensing protein, SCAP, which forms a complex with SREBPs. In sterol- depleted cells, SCAP escorts SREBPs from ER to Golgi, where SREBPs are cleaved by Site-1 protease (S1P). Sterols block this transport and abolish cleavage. Relocating active SIP from Golgi to ER by treating cells with brefeldin A or by fusing the ER retention signal KDEL to S1P obviates the SCAP requirement and renders cleavage insensitive to sterols. Transport- dependent proteolysis may be a common mechanism to regulate the processing of membrane proteins.
AB - Cholesterol homeostasis in animal cells is achieved by regulated cleavage of membrane-bound transcription factors, designated SREBPs. Proteolytic release of the active domains of SREBPs from membranes requires a sterol-sensing protein, SCAP, which forms a complex with SREBPs. In sterol- depleted cells, SCAP escorts SREBPs from ER to Golgi, where SREBPs are cleaved by Site-1 protease (S1P). Sterols block this transport and abolish cleavage. Relocating active SIP from Golgi to ER by treating cells with brefeldin A or by fusing the ER retention signal KDEL to S1P obviates the SCAP requirement and renders cleavage insensitive to sterols. Transport- dependent proteolysis may be a common mechanism to regulate the processing of membrane proteins.
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U2 - 10.1016/S0092-8674(00)81668-2
DO - 10.1016/S0092-8674(00)81668-2
M3 - Article
C2 - 10619424
AN - SCOPUS:0033599028
SN - 0092-8674
VL - 99
SP - 703
EP - 712
JO - Cell
JF - Cell
IS - 7
ER -