title: EML4-ALK fusions: propelling cancer but creating exploitable chaperone dependence.
abstract: The crystal structure of a conserved tubulin-binding region of the EML1 protein reveals a highly atypical fold in one of its β-propeller domains. Disruption of the EML1 core region domain in many of the oncogenic EML4-ALK fusion protein variants that drive non-small cell lung cancer explains their dependence on the HSP90 molecular chaperone, provides a basis to allow more precise patient stratification for therapy, and suggests a more general model for other oncogenic fusion proteins.
authors.affiliation: Authors' Affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom Paul.workman@icr.ac.uk Rob.vanmontfort@icr.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.affiliation: Authors' Affiliation: Cancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom Paul.workman@icr.ac.uk Rob.vanmontfort@icr.ac.uk.
authors.forename: Rob
authors.initials: R
authors.lastname: van Montfort
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: C522504:EML4-ALK fusion protein, human; C000590874:Eml1 protein, human; D018841:HSP90 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion