Formation of alpha-Pal/Max heterodimers synergistically activates the eIF2-alpha promoter.
The transcription factor alpha-Pal recognizes two tandem palindromic repeats within the promoter of eukaryotic translation initiation factor 2-alpha (eIF2-alpha). Whereas both binding sites have the same "core domain" sequence (CGCATGCG), they differ with respect to their flanking sequences. Of the two sites, the 5'-cap proximal site has a higher binding affinity for alpha-Pal than does the 5'-cap distal site (Jacob, W. F., Silverman, T. A., Cohen, R. B., and Safer, B. (1989) J. Biol. Chem. 264, 20372-20384). The well characterized transcription factor Max binds to sequences that are remarkably similar to the core domain that alpha-Pal recognizes. To date, all of the Max heterodimer partners lack DNA binding domains and are thus dependent on Max interacting with DNA. Here we report that the two alpha-Pal sites have very different binding activities with respect to the E-box-binding protein Max. The 5'-cap distal or low alpha-Pal affinity site binds both alpha-Pal and Max. Furthermore, both heterodimers and homodimers of each of these proteins bind to this site. In contrast to the low affinity site, the high affinity site does not bind Max as a homodimer. This is the first documented case where Max heterodimerizes with a transcription factor that has affinity for DNA independent of Max.
Shors
S T
ST
Molecular Hematology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
Efiok
B J
BJ
Harkin
S J
SJ
Safer
B
B
D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D015852:Eukaryotic Initiation Factor-2; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D051266:Nuclear Respiratory Factor 1; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; C067850:Myc associated factor X; D051266:Nuclear Respiratory Factor 1; D014157:Transcription Factors; C088388:alpha-Pal transcription factor