title: Small molecule therapeutics targeting F-box proteins in cancer.
abstract: The ubiquitin proteasome system (UPS) plays vital roles in maintaining protein equilibrium mainly through proteolytic degradation of targeted substrates. The archetypical SCF ubiquitin E3 ligase complex contains a substrate recognition subunit F-box protein that recruits substrates to the catalytic ligase core for its polyubiquitylation and subsequent proteasomal degradation. Several well-characterized F-box proteins have been demonstrated that are tightly linked to neoplasia. There is mounting information characterizing F-box protein-substrate interactions with the rationale to develop unique therapeutics for cancer treatment. Here we review that how F-box proteins function in cancer and summarize potential small molecule inhibitors for cancer therapy.
authors.affiliation: Department of Medicine, The Acute Lung Injury, Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medicine, The Acute Lung Injury, Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240, United States. Electronic address: mallampallirk@upmc.edu.
authors.forename: Rama K
authors.initials: RK
authors.lastname: Mallampalli
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044783:F-Box Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects; D014452:Ubiquitins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D044783:F-Box Proteins; D046912:Multiprotein Complexes; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex
keywords: Cancer; E3 ligase; F-box protein; Small molecule inhibitor; Ubiquitin