The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

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.

Keywords

network / transcription / cancer / MYC / MAX / MLX

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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.).

Compliance with ethics guidelines

Patrick A. Carroll, Brian W. Freie, Haritha Mathsyaraja, and Robert N. Eisenman declare that they have no conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee. Research described from the authors’ laboratory is in full compliance with institutional and national guidelines for the care and use of laboratory animals.

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2018 The Author(s) 2018. This article is published with open access at link.springer.com and journal.hep.com.cn