title: F-box protein interactions with the hallmark pathways in cancer.
abstract: F-box proteins (FBP) are the substrate specifying subunit of Skp1-Cul1-FBP (SCF)-type E3 ubiquitin ligases and are responsible for directing the ubiquitination of numerous proteins essential for cellular function. Due to their ability to regulate the expression and activity of oncogenes and tumour suppressor genes, FBPs themselves play important roles in cancer development and progression. In this review, we provide a comprehensive overview of FBPs and their targets in relation to their interaction with the hallmarks of cancer cell biology, including the regulation of proliferation, epigenetics, migration and invasion, metabolism, angiogenesis, cell death and DNA damage responses. Each cancer hallmark is revealed to have multiple FBPs which converge on common signalling hubs or response pathways. We also highlight the complex regulatory interplay between SCF-type ligases and other ubiquitin ligases. We suggest six highly interconnected FBPs affecting multiple cancer hallmarks, which may prove sensible candidates for therapeutic intervention.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Randle
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. Electronic address: hl316@cam.ac.uk.
authors.forename: Heike
authors.initials: H
authors.lastname: Laman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004249:DNA Damage; D044127:Epigenesis, Genetic; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D044783:F-Box Proteins; D011956:Receptors, Cell Surface
keywords: Cancer hallmarks; E3 ubiquitin ligases; F-box proteins; Signalling; Ubiquitination