Ma A, Moroy T, Collum R, Weintraub H, Alt F W, Blackwell T K
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachussetts 02115.
Oncogene. 1993 Apr;8(4):1093-8.
N- and L-Myc, like c-Myc, contain adjacent basic region (BR), helix-loop-helix (HLH) and leucine zipper (LZ) motifs, which characterize a family of DNA-binding proteins. We have used a polymerase chain reaction (PCR)-based binding site selection technique to demonstrate that the most highly preferred binding site for both N- and L-Myc fusion proteins contains a CACGTG motif, the core binding sequence previously identified for c-Myc. Further analysis identified other N-Myc binding sequences, including asymmetric sequences such as CAT-GTG. N-Myc, like c-Myc, preferentially forms heterodimeric DNA-binding complexes with Max protein. Mutational analyses of N-Myc basic region (BR), helix-loop-helix (HLH) and leucine zipper (LZ) regions revealed that all three regions are necessary for DNA binding by N-Myc-Max complexes, and that dimerization requires both HLH and LZ motifs, while BR sequences are needed only for DNA binding. Our findings support the notion that the LZ motif is a critical element in dimer formation by bHLH-LZ proteins.
与c-Myc一样，N-Myc和L-Myc都含有相邻的碱性区域（BR）、螺旋-环-螺旋（HLH）和亮氨酸拉链（LZ）基序，这些基序是一类DNA结合蛋白的特征。我们使用基于聚合酶链反应（PCR）的结合位点选择技术来证明，N-Myc和L-Myc融合蛋白最优先结合的位点都含有一个CACGTG基序，这是先前确定的c-Myc的核心结合序列。进一步分析确定了其他N-Myc结合序列，包括不对称序列，如CAT-GTG。与c-Myc一样，N-Myc优先与Max蛋白形成异二聚体DNA结合复合物。对N-Myc碱性区域（BR）、螺旋-环-螺旋（HLH）和亮氨酸拉链（LZ）区域的突变分析表明，这三个区域对于N-Myc-Max复合物的DNA结合都是必需的，并且二聚化需要HLH和LZ基序，而BR序列仅用于DNA结合。我们的研究结果支持这样一种观点，即LZ基序是bHLH-LZ蛋白形成二聚体的关键元件。
