Structural and biophysical insights into the function of the intrinsically disordered Myc oncoprotein

Autor: Marie-Eve Beaulieu, Laura Soucek, Francisco Castillo
Přispěvatelé: Institut Català de la Salut, [Beaulieu ME, Castillo F] Peptomyc, Barcelona, Spain. [Soucek L] Peptomyc, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncogens
Leucine zipper
Protein-protein interactions
aminoácidos
péptidos y proteínas::proteínas::proteínas de unión al ADN::factores de transcripción con hélice-asa-hélice básico::proteínas protooncogénicas c-myc [COMPUESTOS QUÍMICOS Y DROGAS]

Drug Evaluation
Preclinical

Biophysics
Computational biology
Review
protein–protein interactions
Myc
Intrinsically disordered proteins
Biophysical Phenomena
Protein–protein interaction
drug discovery
Proto-Oncogene Proteins c-myc
aminoácidos
péptidos y proteínas::proteínas::proteínas intrínsecamente desestructuradas [COMPUESTOS QUÍMICOS Y DROGAS]

03 medical and health sciences
Structure-Activity Relationship
0302 clinical medicine
biophysics
Animals
Humans
Amino Acid Sequence
Nuclear protein
Transcription factor
lcsh:QH301-705.5
Oncogene Proteins
Medicaments - Desenvolupament
Amino Acids
Peptides
and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription Factors::Proto-Oncogene Proteins c-myc [CHEMICALS AND DRUGS]

Oncogene
Drug discovery
Chemistry
Amino Acids
Peptides
and Proteins::Proteins::Intrinsically Disordered Proteins [CHEMICALS AND DRUGS]

General Medicine
ADN - Interaccions de les proteïnes
Investigative Techniques::Drug Development::Drug Evaluation
Preclinical [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES
AND EQUIPMENT]

3. Good health
protein–DNA interactions
Intrinsically Disordered Proteins
técnicas de investigación::desarrollo de medicamentos::evaluación preclínica de medicamentos [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]

030104 developmental biology
lcsh:Biology (General)
030220 oncology & carcinogenesis
Protein-dna interactions
Function (biology)
MAX
Zdroj: Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Scientia
Cells
Cells, Vol 9, Iss 1038, p 1038 (2020)
Popis: Myc; descobriment de fàrmacs; Interaccions proteïna-ADN Myc; Descubrimiento de fármacos; Interacciones proteína-ADN Myc; Drug discovery; Protein–DNA interactions 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. This research was funded by the European Commission (SME Instrument, Grant no. 872212) and European Research Council (CoG grant no. 617473).
Databáze: OpenAIRE