SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis

Xiaodong Wang, Ryuichiro Sato, Michael S. Brown, Xianxin Hua, Joseph L. Goldstein

Research output: Contribution to journalArticle

785 Citations (Scopus)

Abstract

Sterol regulatory element-binding protein 1 (SREBP-1), a member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) family of transcription factors, is synthesized as a 125 kd precursor that is attached to the nuclear envelope and endoplasmic reticulum. In sterol-depleted cells, the membrane-bound precursor is cleaved to generate a soluble NH2-terminal fragment (apparent molecular mass, 68 kd) that translocates to the nucleus. This fragment, which includes the bHLH-ZIP domain, activates transcription of the genes for the LDL receptor and HMG CoA synthase. Sterols inhibit the cleavage of SREBP-1, and the 68 kd nuclear form is rapidly catabolized, thereby reducing transcription. ALLN, an inhibitor of neutral cysteine proteases, blocks the breakdown of the 68 kd form and superinduces sterol-regulated genes. Sterol-regulated proteolysis of a membrane-bound transcription factor provides a novel mechanism by which transcription can be regulated by membrane lipids.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalCell
Volume77
Issue number1
DOIs
StatePublished - Apr 8 1994

Fingerprint

Sterol Regulatory Element Binding Protein 1
Proteolysis
Sterols
Transcription Factors
Transcription
Membranes
Leucine Zippers
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Hydroxymethylglutaryl-CoA Synthase
Genes
Cysteine Proteinase Inhibitors
Cysteine Proteases
LDL Receptors
Nuclear Envelope
Molecular mass
Membrane Lipids
Endoplasmic Reticulum
Cell Membrane

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. / Wang, Xiaodong; Sato, Ryuichiro; Brown, Michael S.; Hua, Xianxin; Goldstein, Joseph L.

In: Cell, Vol. 77, No. 1, 08.04.1994, p. 53-62.

Research output: Contribution to journalArticle

Wang, Xiaodong ; Sato, Ryuichiro ; Brown, Michael S. ; Hua, Xianxin ; Goldstein, Joseph L. / SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. In: Cell. 1994 ; Vol. 77, No. 1. pp. 53-62.
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