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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
Author(s) -
McDuff FrançoisOlivier,
Naud JeanFrançois,
Montagne Martin,
Sauvé Simon,
Lavigne Pierre
Publication year - 2009
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.938
Subject(s) - transcription factor , population , transcription (linguistics) , carcinogenesis , biology , microbiology and biotechnology , gene , chemistry , biochemistry , linguistics , philosophy , demography , sociology
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 © 2009 John Wiley & Sons, Ltd.