title: The Drosophila F-box protein dSkp2 regulates cell proliferation by targeting Dacapo for degradation.
abstract: Cell cycle progression is controlled by a complex regulatory network consisting of interacting positive and negative factors. In humans, the positive regulator Skp2, an F-box protein, has been a subject of intense investigation in part because of its oncogenic activity. By contrast, the molecular and developmental functions of its Drosophila homologue, dSkp2, are poorly understood. Here we investigate the role of dSkp2 by focusing on its functional relationship with Dacapo (Dap), the Drosophila homologue of the cyclin-dependent kinase inhibitors p21(cip1)/p27(kip1)/p57(kip2). We show that dSkp2 interacts physically with Dap and has a role in targeting Dap for ubiquitination and proteasome-mediated degradation. We present evidence that dSkp2 regulates cell cycle progression by antagonizing Dap in vivo. dSkp2 knockdown reduces cell density in the wing by prolonging the cell doubling time. In addition, the wing phenotype caused by dSkp2 knockdown resembles that caused by dap overexpression and can be partially suppressed by reducing the gene dose of dap. Our study thus documents a conserved functional relationship between dSkp2 and Dap in their control of cell cycle progression, suggesting the possibility of using Drosophila as a model system to study Skp2-mediated tumorigenesis.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dui
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
authors.forename: Xuehong
authors.initials: X
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D054875:Ubiquitination; D014921:Wings, Animal / Q000378:metabolism / Q000473:pathology
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D044786:S-Phase Kinase-Associated Proteins; C103336:dap protein, Drosophila; D046988:Proteasome Endopeptidase Complex
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