title: FBXL5 targets cortactin for ubiquitination-mediated destruction to regulate gastric cancer cell migration.
abstract: Cortactin, an actin-interacting protein, is implicated in cytoskeletal architecture and often amplified in several types of cancer including gastric adenocarcinomas. Downregulation of cortactin decreases cell migration and invasion. However, how to regulate cortactin in gastric cancer remains largely unknown. Here, we report that FBXL5 interacts with and targets cortactin for ubiquitylation and subsequent proteasomal degradation. Furthermore, we showed that FBXL5-induced cortactin degradation is mediated by extracellular regulated signal kinase (ERK). Serine phosphorylation sites mutant, cortactinS405A/S418A, prevent FBXL5-induced cortactin degradation. Moreover, CortactinS405A/S418A exhibited stronger effects in promoting gastric cancer cell migration when compared to wild-type cortactin. Taken together, our data suggested a novel molecular mechanism for the negative regulation of cortactin by FBXL5 in gastric cancer cells migration.
authors.affiliation: Department of General Surgery, The First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai, 200080, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cen
authors.forename: Hong-Hua
authors.initials: HH
authors.lastname: Ding
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Wu
mesh_terms: D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis / Q000187:drug effects; D034622:RNA Interference; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C495868:CTTN protein, human; D051356:Cortactin; D044783:F-Box Proteins; C521741:FBXL5 protein, human; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D012694:Serine; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D048049:Extracellular Signal-Regulated MAP Kinases; D046988:Proteasome Endopeptidase Complex; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one