Transport-dependent proteolysis of SREBP: Relocation of Site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi

被引：264

作者：

DeBose-Boyd, RA ^{[1
]}

Brown, MS ^{[1
]}

Li, WP ^{[1
]}

Nohturfft, A ^{[1
]}

Goldstein, JL ^{[1
]}

Espenshade, PJ ^{[1
]}

机构：

[1] Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75216 USA

来源：

CELL | 1999年 / 99卷 / 07期

关键词：

D O I：

10.1016/S0092-8674(00)81668-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 S1P 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.

引用

页码：703 / 712

页数：10

共 37 条

[1]

BOLLAG DM, 1991, PROTEIN METHODS, P1

[2] The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].

Brown, MS ;

Goldstein, JL .

CELL, 1997, 89 (03) :331-340

[3] A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood [J].

Brown, MS ;

Goldstein, JL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (20) :11041-11048

[4] Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins [J].

Cheng, D ;

Espenshade, PJ ;

Slaughter, CA ;

Jaen, JC ;

Brown, MS ;

Goldstein, JL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (32) :22805-22812

[5] Cleavage site for sterol-regulated protease localized to a Leu-Ser bond in the lumenal loop of sterol regulatory element-binding protein-2 [J].

Duncan, EA ;

Brown, MS ;

Goldstein, JL ;

Sakai, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (19) :12778-12785

[6] Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway [J].

Edwards, PA ;

Ericsson, J .

ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :157-185

[7] Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins [J].

Espenshade, PJ ;

Cheng, D ;

Goldstein, JL ;

Brown, MS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (32) :22795-22804

[8]

GOLDSTEIN JL, 1983, METHOD ENZYMOL, V98, P241

[9] Review: Neurobiology - The presenilins in Alzheimer's disease - Proteolysis holds the key [J].

Haass, C ;

De Strooper, B .

SCIENCE, 1999, 286 (5441) :916-919

[10]

HARLOW E, 1999, USING ANTIBODIES LAB, P1

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