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

Russell A. DeBose-Boyd, Michael S. Brown, Wei Ping Li, Axel Nohturfft, Joseph L. Goldstein, Peter J. Espenshade

Research output: Contribution to journalArticle

235 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)703-712
Number of pages10
JournalCell
Volume99
Issue number7
DOIs
StatePublished - Dec 23 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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