SREBP-1, a Membrane-Bound Transcription Factor Released by Sterol-Regulated Proteolysis

Cell. 1994 Apr 8;77(1):53-62. doi: 10.1016/0092-8674(94)90234-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • CCAAT-Enhancer-Binding Proteins*
  • Cell Compartmentation / drug effects
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism
  • Membrane Lipids / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Precursors / metabolism
  • Sterol Regulatory Element Binding Protein 1
  • Sterols / pharmacology*
  • Transcription Factors / metabolism*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Membrane Lipids
  • Membrane Proteins
  • Nuclear Proteins
  • Protein Precursors
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Sterols
  • Transcription Factors