title: Loss of Cul1 results in early embryonic lethality and dysregulation of cyclin E.
abstract: The sequential timing of cell-cycle transitions is primarily governed by the availability and activity of key cell-cycle proteins. Recent studies in yeast have identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote and inhibit cell-cycle progression at the G1-S phase transition. SCF complexes consist of three invariable components, Skp1, Cul-1 (Cdc53 in yeast) and Rbx1, and a variable F-box protein that recruits a specific cellular protein to the ubquitin pathway for degradation. To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines. We show that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (encoded by Ccne), during embryogenesis.
authors.affiliation: Department of Biology, University of California, San Diego, California 92093-0366, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Dealy
authors.forename: K V
authors.initials: KV
authors.lastname: Nguyen
authors.forename: J
authors.initials: J
authors.lastname: Lo
authors.forename: M
authors.initials: M
authors.lastname: Gstaiger
authors.forename: W
authors.initials: W
authors.lastname: Krek
authors.forename: D
authors.initials: D
authors.lastname: Elson
authors.forename: J
authors.initials: J
authors.lastname: Arbeit
authors.forename: E T
authors.initials: ET
authors.lastname: Kipreos
authors.forename: R S
authors.initials: RS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D044842:Cullin Proteins; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D005313:Fetal Death / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C100988:Cdc53 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D019927:Cyclin E; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53