A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins.
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.
Virbasius
C M
CM
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605, USA.
Wagner
S
S
Green
M R
MR
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
C105242:ALYREF protein, human; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D013884:Thiosulfate Sulfurtransferase