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Centrosomes organize the mitotic spindle to ensure accurate segregation of the chromosomes in mitosis. The mechanism that ensures accurate duplication and separation of the centrosomes underlies the fidelity of chromosome segregation, but remains unknown. In Saccharomyces cerevisiae, entry into S phase and separation of spindle pole bodies each require CDC4 and CDC34, which encode components of an SCF (Skp1-cullin-F-box) ubiquitin ligase, but a direct (SCF) connection to the spindle pole body is unknown. Using immunofluorescence microscopy, we show that in mammalian cells the Skp1 protein and the cullin Cul1 are localized to interphase and mitotic centrosomes and to the cytoplasm and nucleus. Deconvolution and immunoelectron microscopy suggest that Skp1 forms an extended pericentriolar structure that may function to organize the centrosome. Purified centrosomes also contain Skp1, and Cul1 modified by the ubiquitin-like molecule NEDD8, suggesting a role for NEDD8 in targeting. Using an in vitro assay for centriole separation in Xenopus extracts, antibodies to Skp1 or Cul1 block separation. Proteasome inhibitors block both centriole separation in vitro and centrosome duplication in Xenopus embryos. We identify candidate centrosomal F-box proteins, suggesting that distinct SCF complexes may direct proteolysis of factors mediating multiple steps in the centrosome cycle.
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10485847 ???displayArticle.pmcLink???PMC316987 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Agard,
Fluorescence microscopy in three dimensions.
1989, Pubmed
Agard,
Fluorescence microscopy in three dimensions.
1989,
Pubmed Bai,
SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
1996,
Pubmed Balczon,
Dissociation of centrosome replication events from cycles of DNA synthesis and mitotic division in hydroxyurea-arrested Chinese hamster ovary cells.
1995,
Pubmed Bornens,
Structural and chemical characterization of isolated centrosomes.
1987,
Pubmed
,
Xenbase Bouckson-Castaing,
Molecular characterisation of ninein, a new coiled-coil protein of the centrosome.
1996,
Pubmed Broek,
Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.
1991,
Pubmed Correa-Bordes,
p25rum1 orders S phase and mitosis by acting as an inhibitor of the p34cdc2 mitotic kinase.
1995,
Pubmed Dahmann,
S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state.
1995,
Pubmed Dictenberg,
Pericentrin and gamma-tubulin form a protein complex and are organized into a novel lattice at the centrosome.
1998,
Pubmed
,
Xenbase Doxsey,
Pericentrin, a highly conserved centrosome protein involved in microtubule organization.
1994,
Pubmed
,
Xenbase Drury,
The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast.
1997,
Pubmed Dutta,
Initiation of DNA replication in eukaryotic cells.
1997,
Pubmed Fang,
Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes.
1991,
Pubmed
,
Xenbase Feldman,
A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.
1997,
Pubmed Fenteany,
Lactacystin, proteasome function, and cell fate.
1998,
Pubmed Fry,
A centrosomal function for the human Nek2 protein kinase, a member of the NIMA family of cell cycle regulators.
1998,
Pubmed Fry,
C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2.
1998,
Pubmed Fukasawa,
Abnormal centrosome amplification in the absence of p53.
1996,
Pubmed Gard,
Centrosome duplication continues in cycloheximide-treated Xenopus blastulae in the absence of a detectable cell cycle.
1990,
Pubmed
,
Xenbase Geissler,
The spindle pole body component Spc98p interacts with the gamma-tubulin-like Tub4p of Saccharomyces cerevisiae at the sites of microtubule attachment.
1996,
Pubmed Glas,
A proteolytic system that compensates for loss of proteasome function.
1998,
Pubmed Glover,
Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles.
1995,
Pubmed Goebl,
The Ubc3 (Cdc34) ubiquitin-conjugating enzyme is ubiquitinated and phosphorylated in vivo.
1994,
Pubmed Handeli,
The ts41 mutation in Chinese hamster cells leads to successive S phases in the absence of intervening G2, M, and G1.
1992,
Pubmed Hinchcliffe,
Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts.
1999,
Pubmed
,
Xenbase Hinchcliffe,
The coordination of centrosome reproduction with nuclear events of the cell cycle in the sea urchin zygote.
1998,
Pubmed Hochstrasser,
Ubiquitin-dependent protein degradation.
1996,
Pubmed Jackson,
Early events in DNA replication require cyclin E and are blocked by p21CIP1.
1995,
Pubmed
,
Xenbase Jallepalli,
sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins for degradation and stops unwanted diploidization in fission yeast.
1998,
Pubmed Kamitani,
Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein.
1997,
Pubmed Kaplan,
Regulating the yeast kinetochore by ubiquitin-dependent degradation and Skp1p-mediated phosphorylation.
1997,
Pubmed Kellogg,
The centrosome and cellular organization.
1994,
Pubmed Kipreos,
cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family.
1996,
Pubmed Knop,
Spc98p and Spc97p of the yeast gamma-tubulin complex mediate binding to the spindle pole body via their interaction with Spc110p.
1997,
Pubmed Koepp,
How the cyclin became a cyclin: regulated proteolysis in the cell cycle.
1999,
Pubmed Kominami,
Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18.
1997,
Pubmed Kuriyama,
Centriole cycle in Chinese hamster ovary cells as determined by whole-mount electron microscopy.
1981,
Pubmed Lacey,
Cyclin-dependent kinase control of centrosome duplication.
1999,
Pubmed
,
Xenbase Lammer,
Modification of yeast Cdc53p by the ubiquitin-related protein rub1p affects function of the SCFCdc4 complex.
1998,
Pubmed Lane,
Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.
1996,
Pubmed Laney,
Substrate targeting in the ubiquitin system.
1999,
Pubmed Liakopoulos,
Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function.
1999,
Pubmed Lingle,
Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity.
1998,
Pubmed Lisztwan,
Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway.
1998,
Pubmed Lyapina,
Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein.
1998,
Pubmed Marti,
Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation.
1999,
Pubmed Martin,
Xgrip109: a gamma tubulin-associated protein with an essential role in gamma tubulin ring complex (gammaTuRC) assembly and centrosome function.
1998,
Pubmed
,
Xenbase Mathias,
Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1-to-S-phase transition and identifies a conserved family of proteins.
1996,
Pubmed Matsumoto,
Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells.
1999,
Pubmed McDonald,
A proteasome cap subunit required for spindle pole body duplication in yeast.
1997,
Pubmed Meraldi,
Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A.
1999,
Pubmed Mitchison,
Isolation of mammalian centrosomes.
1986,
Pubmed Montagnoli,
Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.
1999,
Pubmed Moritz,
Microtubule nucleation by gamma-tubulin-containing rings in the centrosome.
1995,
Pubmed Moritz,
Three-dimensional structural characterization of centrosomes from early Drosophila embryos.
1995,
Pubmed Moritz,
Recruitment of the gamma-tubulin ring complex to Drosophila salt-stripped centrosome scaffolds.
1998,
Pubmed
,
Xenbase Murphy,
The mammalian gamma-tubulin complex contains homologues of the yeast spindle pole body components spc97p and spc98p.
1998,
Pubmed
,
Xenbase Oegema,
Two proteins that cycle asynchronously between centrosomes and nuclear structures: Drosophila CP60 and CP190.
1997,
Pubmed Oegema,
The cell cycle-dependent localization of the CP190 centrosomal protein is determined by the coordinate action of two separable domains.
1995,
Pubmed Osaka,
A new NEDD8-ligating system for cullin-4A.
1998,
Pubmed Paintrand,
Centrosome organization and centriole architecture: their sensitivity to divalent cations.
1992,
Pubmed Patton,
Combinatorial control in ubiquitin-dependent proteolysis: don't Skp the F-box hypothesis.
1998,
Pubmed Peters,
SCF and APC: the Yin and Yang of cell cycle regulated proteolysis.
1998,
Pubmed Pihan,
Centrosome defects and genetic instability in malignant tumors.
1998,
Pubmed Schnackenberg,
The disassembly and reassembly of functional centrosomes in vitro.
1998,
Pubmed Schwob,
The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
1994,
Pubmed Skowyra,
F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
1997,
Pubmed Skowyra,
Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1.
1999,
Pubmed Sluder,
Protein synthesis and the cell cycle: centrosome reproduction in sea urchin eggs is not under translational control.
1990,
Pubmed Stearns,
In vitro reconstitution of centrosome assembly and function: the central role of gamma-tubulin.
1994,
Pubmed
,
Xenbase Stearns,
Gamma-tubulin is a highly conserved component of the centrosome.
1991,
Pubmed
,
Xenbase Stemmann,
The Saccharomyces cerevisiae kinetochore contains a cyclin-CDK complexing homologue, as identified by in vitro reconstitution.
1996,
Pubmed Stillman,
Cell cycle control of DNA replication.
1996,
Pubmed Strausfeld,
Cip1 blocks the initiation of DNA replication in Xenopus extracts by inhibition of cyclin-dependent kinases.
1994,
Pubmed
,
Xenbase Su,
Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1.
1995,
Pubmed
,
Xenbase Tassin,
Characterization of the human homologue of the yeast spc98p and its association with gamma-tubulin.
1998,
Pubmed
,
Xenbase Tsvetkov,
p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.
1999,
Pubmed Verma,
Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase.
1997,
Pubmed Wada,
Identification of NEDD8-conjugation site in human cullin-2.
1999,
Pubmed Wigley,
Dynamic association of proteasomal machinery with the centrosome.
1999,
Pubmed Willems,
Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway.
1996,
Pubmed Winey,
MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication.
1991,
Pubmed Winey,
Assembly and functions of the spindle pole body in budding yeast.
1993,
Pubmed Wolf,
F-box/WD-repeat proteins pop1p and Sud1p/Pop2p form complexes that bind and direct the proteolysis of cdc18p.
1999,
Pubmed Wolf,
Cell cycle: oiling the gears of anaphase.
1998,
Pubmed Yew,
Proteolysis and DNA replication: the CDC34 requirement in the Xenopus egg cell cycle.
1997,
Pubmed
,
Xenbase Yu,
Identification of a cullin homology region in a subunit of the anaphase-promoting complex.
1998,
Pubmed Zachariae,
Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins.
1998,
Pubmed Zhang,
p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase.
1995,
Pubmed Zheng,
Gamma-tubulin is present in Drosophila melanogaster and Homo sapiens and is associated with the centrosome.
1991,
Pubmed Zheng,
Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex.
1995,
Pubmed
,
Xenbase Zimmerman,
Amorphous no longer: the centrosome comes into focus.
1999,
Pubmed
