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

230 Citations (Scopus)

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
StatePublished - Dec 23 1999

Fingerprint

Proteolysis
Relocation
Sterols
Membranes
Brefeldin A
Membrane Proteins
Animals
Homeostasis
Transcription Factors
Cholesterol
Cells
site 1 membrane-bound transcription factor peptidase
Processing
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Transport-dependent proteolysis of SREBP : Relocation of Site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. / DeBose-Boyd, Russell A.; Brown, Michael S.; Li, Wei Ping; Nohturfft, Axel; Goldstein, Joseph L.; Espenshade, Peter J.

In: Cell, Vol. 99, No. 7, 23.12.1999, p. 703-712.

Research output: Contribution to journalArticle

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