The Max homodimeric b-HLH-LZ significantly interferes with the specific heterodimerization between the c-Myc and Max b-HLH-LZ in absence of DNA: a quantitative analysis
The Max homodimeric b-HLH-LZ significantly interferes with the specific heterodimerization between the c-Myc and Max b-HLH-LZ in absence of DNA: a quantitative analysis
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DOI：
10.1002/jmr.938
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发表时间：
2009-07-01
影响因子：
2.7
通讯作者：
Lavigne, Pierre
中科院分区：
文献类型：
--
作者：
McDuff, Francois-Olivier;Naud, Jean-Franois;Lavigne, Pierre
特异性异源二聚化在细胞生物学的调节中起着至关重要的作用。例如，b-HLH-LZ转录因子c-Myc和Max之间的特异性异源二聚化是导致细胞生长、增殖和肿瘤发生的c-Myc转录活性的先决条件。另一方面，Mad蛋白可以与c-Myc竞争Max。Mad/Max异二聚体拮抗c-Myc/Max异二聚体的作用。在这方面的贡献，我们集中在特定的异源二聚体之间的b-HLH-LZ域的c-Myc和马克斯使用CD和NMR。虽然发现c-Myc和Max b-HLH-LZ结构域优先形成异二聚体，但我们首次证明了Max同二聚体b-HLH-LZ的显著群体也可以形成，因此显著干扰特异性异二聚化。这表明Max/Max同源二聚体也可以干扰c-Myc/Max功能，因此增加了Myc/Max/Mad网络调控转录的复杂性。通过应用数值程序可以证明同源二聚体群体的存在，该数值程序能够模拟作为温度和蛋白质总浓度的函数的复合光谱信号（例如CD）。从系统生物学的角度来看，我们的程序可能会引起普遍兴趣，因为它们提供了处理许多竞争平衡的机会，以预测蛋白质复合物存在的概率。版权所有（C）2009约翰威利父子有限公司
Specific heterodimerization plays a crucial role in the regulation of the biology of the cell. For example, the specific heterodimerization between the b-HLH-LZ transcription factors c-Myc and Max is a prerequisite for c-Myc transcriptional activity that leads to cell growth, proliferation and tumorigenesis. On the other hand, the Mad proteins can compete with c-Myc for Max. The Mad/Max heterodimer antagonizes the effect of the c-Myc/Max heterodimer. In this contribution, we have focused on the specific heterodimerization between the b-HLH-LZ domains of c-Myc and Max using CD and NMR. While the c-Myc and Max b-HLH-LZ domains are found to preferentially form a heterodimer; we demonstrate for the first time that a significant population of the Max homodimeric b-HLH-LZ can also form and hence interferes significantly with the specific heterodimerization. This indicates that the Max/Max homodimer can also interfere with c-Myc/Max functions, therefore adding to the complexity of the regulation of transcription by the Myc/Max/Mad network. The demonstration of the existence of the homodimeric population was made possible by the application of numerical routines that enable the simulation of composite spectroscopic signal (e.g. CD) as a function of temperature and total concentration of proteins. From a systems biology perspective, our routines may be of general interest as they offer the opportunity to treat many competing equilibriums in order to predict the probability of existence of protein complexes. Copyright (C) 2009 John Wiley & Sons, Ltd.