Prochownik E V, VanAntwerp M E
Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor 48109.
Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):960-4. doi: 10.1073/pnas.90.3.960.
c-myc, N-myc, and L-myc genes are subject to highly variable degrees of tissue-specific regulation. Their aberrant expression has also been implicated in the pathogenesis of a variety of malignant tumors. The recently identified max protein dimerizes with c-myc to promote its sequence-specific DNA binding. max exists in two forms (long and short) that differ by virtue of a 9-amino acid insertion/deletion at the N terminus. We tested recombinant myc and max proteins for binding to six oligonucleotides containing related c-myc sites. Each myc protein, alone and in association with max proteins, manifested a unique pattern of DNA binding. Phosphorylation of both max proteins was observed when they were incubated in a rabbit reticulocyte lysate. This strongly affected DNA binding by max(long) but not by max(short). Our results point to the existence of specific DNA binding preferences for each of the myc proteins. The 9-amino acid segment that distinguishes max(long) from max(short) appears to serve a regulatory function that provides additional control over DNA sequence recognition.
c-myc、N-myc和L-myc基因受到高度可变程度的组织特异性调控。它们的异常表达也与多种恶性肿瘤的发病机制有关。最近发现的Max蛋白与c-myc二聚化以促进其序列特异性DNA结合。Max存在两种形式(长型和短型),它们在N端因9个氨基酸的插入/缺失而有所不同。我们测试了重组Myc和Max蛋白与六个含有相关c-myc位点的寡核苷酸的结合情况。每种Myc蛋白单独以及与Max蛋白结合时,都表现出独特的DNA结合模式。当将两种Max蛋白在兔网织红细胞裂解物中孵育时,观察到它们都发生了磷酸化。这对Max(长型)的DNA结合有强烈影响,但对Max(短型)没有影响。我们的结果表明每种Myc蛋白都存在特定的DNA结合偏好。区分Max(长型)和Max(短型)的9个氨基酸片段似乎起到一种调节功能,对DNA序列识别提供额外的控制。