A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins

Mol Cell. 1999 Aug;4(2):219-28. doi: 10.1016/s1097-2765(00)80369-x.


We have identified and cloned a human nuclear protein that dramatically increases DNA binding of transcription factors that contain a basic region-leucine zipper (bZIP) DNA binding domain. We show that this bZIP enhancing factor (BEF) functions as a molecular chaperone. BEF stimulates DNA binding by recognizing the unfolded leucine zipper and promoting the folding of bZIP monomers to dimers; the elevated concentration of the bZIP dimer then drives the DNA binding reaction. Antisense experiments indicate that BEF is required for efficient transcriptional activation by bZIP proteins in vivo. Our results reveal protein folding in the nucleus as a step at which sequence-specific DNA binding proteins can be regulated.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism*
  • Cloning, Molecular
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dimerization
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Leucine Zippers
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Protein Folding
  • RNA-Binding Proteins*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Thiosulfate Sulfurtransferase / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Transfection


  • ALYREF protein, human
  • DNA-Binding Proteins
  • Molecular Chaperones
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Thiosulfate Sulfurtransferase