Structural and biophysical insights into the function of the intrinsically disordered Myc oncoprotein
Autor: | Marie-Eve Beaulieu, Laura Soucek, Francisco Castillo |
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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 |
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