title: Myc and its interactors take shape.
abstract: The Myc oncoprotein is a key contributor to the development of many human cancers. As such, understanding its molecular activities and biological functions has been a field of active research since its discovery more than three decades ago. Genome-wide studies have revealed Myc to be a global regulator of gene expression. The identification of its DNA-binding partner protein, Max, launched an area of extensive research into both the protein-protein interactions and protein structure of Myc. In this review, we highlight key insights with respect to Myc interactors and protein structure that contribute to the understanding of Myc's roles in transcriptional regulation and cancer. Structural analyses of Myc show many critical regions with transient structures that mediate protein interactions and biological functions. Interactors, such as Max, TRRAP, and PTEF-b, provide mechanistic insight into Myc's transcriptional activities, while others, such as ubiquitin ligases, regulate the Myc protein itself. It is appreciated that Myc possesses a large interactome, yet the functional relevance of many interactors remains unknown. Here, we discuss future research trends that embrace advances in genome-wide and proteome-wide approaches to systematically elucidate mechanisms of Myc action. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: William B
authors.initials: WB
authors.lastname: Tu
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Helander
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Pilstål
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: K Ashley
authors.initials: KA
authors.lastname: Hickman
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Corey
authors.initials: C
authors.lastname: Lourenco
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Raught
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Wallner
authors.affiliation: Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Sunnerhagen
authors.affiliation: Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address: lpenn@uhnres.utoronto.ca.
authors.forename: Linda Z
authors.initials: LZ
authors.lastname: Penn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D060066:Protein Interaction Maps / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D020543:Proteome; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C489427:MYC protein, human; D009687:Nuclear Proteins; D020543:Proteome; D016271:Proto-Oncogene Proteins c-myc; C113829:transformation-transcription domain-associated protein
keywords: Cancer; Myc; Post-translational modification; Protein structure; Protein–protein interaction; Transcriptional regulation