Kerppola T K, Curran T
Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Oncogene. 1994 Nov;9(11):3149-58.
The c-maf proto-oncogene and the neural retina specific gene nrl encode members of a subfamily of bZIP proteins that form heterodimers with Fos and Jun. We have determined the DNA binding specificities of various homo- and heterodimeric combinations among Nrl, Maf, Fos and Jun. Fos-Jun heterodimers and Jun homodimers bound to a palindromic TGAC(G)TCA recognition sequence as previously demonstrated. Maf and Nrl homodimers also bound to palindromic recognition sites with the consensus sequence TGC(N)6-7GCA. Fos-Nrl, Jun-Nrl and Fos-Maf heterodimers bound to nonpalindromic recognition sequences with the consensus sequence TGAC(N)3-4GCA. These results indicate that Nrl and Maf have a DNA binding specificity distinct from that of Fos and Jun, and that each subunit in the dimer independently recognizes one half of the recognition sequence. This allows combinatorial determination of target gene specificity. Specific recognition of the extended DNA binding sequence by Maf requires an ancillary DNA binding region on the amino terminal side of the basic domain that is conserved among Maf/Nrl family members. Thus, heterodimer formation among distantly related bZIP family members can generate novel DNA binding specificities and the addition of an auxiliary DNA binding domain to the simple bZIP motif can facilitate the recognition of extended binding sites.
c-maf原癌基因和神经视网膜特异性基因nrl编码bZIP蛋白亚家族的成员，这些成员与Fos和Jun形成异二聚体。我们已经确定了Nrl、Maf、Fos和Jun之间各种同二聚体和异二聚体组合的DNA结合特异性。如先前所示，Fos-Jun异二聚体和Jun同二聚体与回文TGAC(G)TCA识别序列结合。Maf和Nrl同二聚体也与共有序列为TGC(N)6-7GCA的回文识别位点结合。Fos-Nrl、Jun-Nrl和Fos-Maf异二聚体与共有序列为TGAC(N)3-4GCA的非回文识别序列结合。这些结果表明，Nrl和Maf具有与Fos和Jun不同的DNA结合特异性，并且二聚体中的每个亚基独立识别识别序列的一半。这允许对靶基因特异性进行组合确定。Maf对扩展DNA结合序列的特异性识别需要在碱性结构域氨基末端侧的一个辅助DNA结合区域，该区域在Maf/Nrl家族成员中是保守的。因此，远缘相关bZIP家族成员之间的异二聚体形成可以产生新的DNA结合特异性，并且在简单的bZIP基序上添加一个辅助DNA结合结构域可以促进对扩展结合位点的识别。
