SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene

Cell. 1993 Oct 8;75(1):187-97.


Sterol regulatory element 1 (SRE-1), a decamer (5'-ATC-ACCCCAC-3') flanking the low density lipoprotein (LDL) receptor gene, activates transcription in sterol-depleted cells and is silenced by sterols. We report the cDNA cloning of human SREBP-1, a protein that binds SRE-1, activates transcription, and thereby mediates the final regulatory step in LDL metabolism. SREBP-1 contains a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) motif, but it differs from other bHLH-ZIP proteins in its larger size (1147 amino acids) and target sequence. Instead of an inverted repeat (CANNTG), the target for all known bHLH-ZIP proteins, SRE-1 contains a direct repeat of CAC. Overexpression of SREBP-1 activates transcription of reporter genes containing SRE-1 in the absence (15-fold) and presence (90-fold) of sterols, abolishing sterol regulation. We suggest that SREBP-1 is regulated by an unknown factor that is overwhelmed when SREBP-1 is overexpressed. Understanding the regulation of SREBP-1 may be crucial for understanding the control of plasma cholesterol in humans.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • CCAAT-Enhancer-Binding Proteins*
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • HeLa Cells
  • Helix-Loop-Helix Motifs*
  • Humans
  • Leucine Zippers*
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Receptors, LDL / biosynthesis*
  • Receptors, LDL / genetics*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid*
  • Repetitive Sequences, Nucleic Acid
  • Sequence Homology, Amino Acid
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors*
  • Transcription, Genetic


  • CCAAT-Enhancer-Binding Proteins
  • DNA Primers
  • DNA, Complementary
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Receptors, LDL
  • Recombinant Proteins
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors

Associated data

  • GENBANK/L20888
  • GENBANK/L20889
  • GENBANK/L26083
  • GENBANK/L33709
  • GENBANK/S60904
  • GENBANK/S60905
  • GENBANK/S60924
  • GENBANK/S66167
  • GENBANK/S66168
  • GENBANK/U00968