High impact information on Max

• Myc acts through dimerization with Max to bind DNA and activate transcription [1].
• These findings indicate a potential role for Myc in germ cell development and set the stage for genetic analysis of Myc and Max [1].
• Homologs of the myc and max genes were cloned from the fruit fly Drosophila melanogaster and their protein products (dMyc and dMax) were shown to heterodimerize, recognize the same DNA sequence as their vertebrate homologs, and activate transcription [1].
• These results suggest that a fundamental aspect of Max network function involves widespread binding and regulation of gene expression [2].
• The Myc/Max/Mad transcription factor network is critically involved in cell behavior; however, there is relatively little information on its genomic binding sites [2].

Biological context of Max

• Structural conservation in regions of known functional significance is consistent with the ability of dMyc1 to interact with vertebrate Max, to transactivate gene expression in yeast cells, and to cooperate with activated H-RAS to effect the malignant transformation of primary mammalian cells [3].
• The identification of Myc and Max homologs in Drosophila melanogaster has demonstrated a critical role for dMyc in cell growth control [4].
• The Mlx network: evidence for a parallel Max-like transcriptional network that regulates energy metabolism [5].
• Similar to Max-containing heterodimers, Mlx-containing heterodimers recognize CACGTG E-box elements, suggesting that the transcriptional targets of these two networks may overlap [5].
• The Myc proto-oncogenes, their binding partner Max and their antagonists from the Mad family of transcriptional repressors have been extensively analysed in vertebrates [6].

Physical interactions of Max

• The N-termini of xPontin and xReptin, which mediate the mitogenic effect were mapped to contain c-Myc interaction domains. c-Myc protein promotes cell cycle progression either by transcriptional activation through the c-Myc/Max complex or by repression of cyclin dependent kinase inhibitors (p21, p15) through c-Myc/Miz-1 interaction [7].

Regulatory relationships of Max

• This approach also reveals dynamic interactions among network members as we find that increased levels of dMax influence the extent of dMyc, but not dMnt, binding [2].

Other interactions of Max

• Like Max, Mix interacts with transcriptional repressors and transcriptional activators, namely the Mad family and the Mondo family, respectively [5].

References