Structural and biophysical insights into the function of the intrinsically disordered Myc oncoprotein
Beaulieu, Marie-Eve (Peptomyc S.L.)
Castillo, Francisco (Peptomyc S.L.)
Soucek, Laura (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2020
Abstract:	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.
Grants:	European Commission 872212 European Commission 617473
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Myc ; MAX ; Protein-protein interactions ; Protein-dna interactions ; Intrinsically disordered proteins ; Biophysics ; Drug discovery
Published in:	Cells, Vol. 9, Issue 4 (April 2020) , art. 1038, ISSN 2073-4409

DOI: 10.3390/cells9041038
PMID: 32331235

27 p, 2.3 MB

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