Shors S T, Efiok B J, Harkin S J, Safer B
Molecular Hematology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 1998 Dec 25;273(52):34703-9. doi: 10.1074/jbc.273.52.34703.
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.
转录因子α-Pal可识别真核生物翻译起始因子2-α（eIF2-α）启动子内的两个串联回文重复序列。尽管两个结合位点具有相同的“核心结构域”序列（CGCATGCG），但其侧翼序列不同。在这两个位点中，5'-帽近端位点对α-Pal的结合亲和力高于5'-帽远端位点（雅各布，W.F.，西尔弗曼，T.A.，科恩，R.B.，和萨弗，B.（1989年）《生物化学杂志》264卷，20372 - 20384页）。特征明确的转录因子Max可结合与α-Pal识别的核心结构域非常相似的序列。迄今为止，所有Max异二聚体伙伴都缺乏DNA结合结构域，因此依赖于Max与DNA相互作用。在此我们报告，关于E盒结合蛋白Max，α-Pal的两个位点具有非常不同的结合活性。5'-帽远端或低α-Pal亲和力位点可结合α-Pal和Max。此外，这些蛋白质各自的异二聚体和同二聚体都可结合该位点。与低亲和力位点相反，高亲和力位点不能结合作为同二聚体的Max。这是首次有文献记载的Max与一种对DNA具有独立于Max的亲和力的转录因子形成异二聚体的情况。
