Structural and Biophysical Insights into the Function of the Intrinsically Disordered Myc Oncoprotein.
Marie-Eve BeaulieuFrancisco CastilloLaura SoucekPublished in: Cells (2020)
Myc is a transcription factor driving growth and proliferation of cells and involved in the majority of human tumors. Despite a huge body of literature on this critical oncogene, our understanding of the exact molecular determinants and mechanisms that underlie its function is still surprisingly limited. Indubitably though, its crucial and non-redundant role in cancer biology makes it an attractive target. However, achieving successful clinical Myc inhibition has proven challenging so far, as this nuclear protein is an intrinsically disordered polypeptide devoid of any classical ligand binding pockets. Indeed, Myc only adopts a (partially) folded structure in some contexts and upon interacting with some protein partners, for instance when dimerizing with MAX to bind DNA. Here, we review the cumulative knowledge on Myc structure and biophysics and discuss the implications for its biological function and the development of improved Myc inhibitors. We focus this biophysical walkthrough mainly on the basic region helix-loop-helix leucine zipper motif (bHLHLZ), as it has been the principal target for inhibitory approaches so far.
Keyphrases
- transcription factor
- dna binding
- healthcare
- systematic review
- induced apoptosis
- signaling pathway
- cell free
- single molecule
- protein protein
- oxidative stress
- binding protein
- papillary thyroid
- small molecule
- men who have sex with men
- cell proliferation
- circulating tumor
- cell cycle arrest
- molecular dynamics
- antiretroviral therapy