Abstract
Transcription factor networks have evolved in order to control, coordinate, and separate, the functions of distinct network modules spatially and temporally. In this review we focus on the MYC network (also known as the MAX-MLX Network), a highly conserved super-family of related basic-helix-loop-helix-zipper (bHLHZ) proteins that functions to integrate extracellular and intracellular signals and modulate global gene expression. Importantly the MYC network has been shown to be deeply involved in a broad spectrum of human and other animal cancers. Here we summarize molecular and biological properties of the network modules with emphasis on functional interactions among network members. We suggest that these network interactions serve to modulate growth and metabolism at the transcriptional level in order to balance nutrient demand with supply, to maintain growth homeostasis, and to influence cell fate. Moreover, oncogenic activation of MYC and/or loss of a MYC antagonist, results in an imbalance in the activity of the network as a whole, leading to tumor initiation, progression and maintenance.
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Acknowledgements
The authors thank Daniel Diolaiti, Don Ayer, and Peter Hurlin as well as other past and present members of the Eisenman laboratory for many discussions concerning MYC and its network. Research conducted by the authors mentioned in this review was supported by grants from NIH/NCI (Nos. RO1CA20525 and RO1CA57138) and a Hartwell Innovation Fund Pilot grant (to R.N.E.).
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Carroll, P.A., Freie, B.W., Mathsyaraja, H. et al. The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis. Front. Med. 12, 412–425 (2018). https://doi.org/10.1007/s11684-018-0650-z
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DOI: https://doi.org/10.1007/s11684-018-0650-z