title: F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
abstract: Fbxl7, a subunit of the SCF (Skp-Cul1-F-box protein) complex induces mitotic arrest in cells; however, molecular factors that control its cellular abundance remain largely unknown. Here, we identified that an orphan F-box protein, Fbxl18, targets Fbxl7 for its polyubiquitylation and proteasomal degradation. Lys 109 within Fbxl7 is an essential acceptor site for ubiquitin conjugation by Fbxl18. An FQ motif within Fbxl7 serves as a molecular recognition site for Fbxl18 interaction. Ectopically expressed Fbxl7 induces apoptosis in Hela cells, an effect profoundly accentuated after cellular depletion of Fbxl18 protein or expression of Fbxl7 plasmids encoding mutations at either Lys 109 or within the FQ motif. Ectopic expression of Fbxl18 plasmid-limited apoptosis caused by overexpressed Fbxl7 plasmid. Thus, Fbxl18 regulates apoptosis by mediating ubiquitin-dependent proteasomal degradation of the pro-apoptotic protein Fbxl7 that may impact cellular processes involved in cell cycle progression.
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Y
authors: Y
authors: Liu
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: T
authors: T
authors: Lear
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Y
authors: Y
authors: Zhao
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: J
authors: J
authors: Zhao
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: C
authors: C
authors: Zou
authors: Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
authors: B B
authors: BB
authors: Chen
authors: 1] Department of Medicine, the Acute Lung Injury Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA [2] Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors: R K
authors: RK
authors: Mallampalli
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins; D044783:F-Box Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D051379:Mice; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D008239:Lysine; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits; C499971:FBXL19 protein, human; C529982:FBXL7 protein, human
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