Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Mol Biol Cell
1995 Feb 01;62:185-97. doi: 10.1091/mbc.6.2.185.
Show Gene links
Show Anatomy links
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
Sudakin V
,
Ganoth D
,
Dahan A
,
Heller H
,
Hershko J
,
Luca FC
,
Ruderman JV
,
Hershko A
.
???displayArticle.abstract???
The ubiquitin-mediated degradation of mitotic cyclins is required for cells to exit from mitosis. Previous work with cell-free systems has revealed four components required for cyclin-ubiquitin ligation and proteolysis: a nonspecific ubiquitin-activating enzyme E1, a soluble fraction containing a ubiquitin carrier protein activity called E2-C, a crude particulate fraction containing a ubiquitin ligase (E3) activity that is activated during M-phase, and a constitutively active 26S proteasome that degrades ubiquitinated proteins. Here, we identify a novel approximately 1500-kDa complex, termed the cyclosome, which contains a cyclin-selective ubiquitin ligase activity, E3-C. E3-C is present but inactive during interphase; it can be activated in vitro by the addition of cdc2, enabling the transfer of ubiquitin from E2-C to cyclin. The kinetics of E3-C activation suggest the existence of one or more intermediates between cdc2 and E3-C. Cyclosome-associated E3-C acts on both cyclin A and B, and requires the presence of wild-type N-terminal destruction box motifs in each cyclin. Ubiquitinated cyclins are then rapidly recognized and degraded by the proteasome. These results identify the cyclosome-associated E3-C as the component of the cyclin destruction machinery whose activity is ultimately regulated by cdc2 and, as such, the element directly responsible for setting mitotic cyclin levels during early embryonic cell cycles.
Bartel,
The recognition component of the N-end rule pathway.
1990, Pubmed
Bartel,
The recognition component of the N-end rule pathway.
1990,
Pubmed
Ciechanover,
Degradation of nuclear oncoproteins by the ubiquitin system in vitro.
1991,
Pubmed
Dohmen,
The N-end rule is mediated by the UBC2(RAD6) ubiquitin-conjugating enzyme.
1991,
Pubmed
Evans,
Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division.
1983,
Pubmed
,
Echinobase
Finley,
Ubiquitination.
1991,
Pubmed
Félix,
Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase.
1990,
Pubmed
,
Echinobase
Gallant,
Cyclin B2 undergoes cell cycle-dependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells.
1992,
Pubmed
Ghiara,
A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis.
1991,
Pubmed
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
Hartwell,
Checkpoints: controls that ensure the order of cell cycle events.
1989,
Pubmed
Heller,
A ubiquitin-protein ligase specific for type III protein substrates.
1990,
Pubmed
Hershko,
Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown.
1983,
Pubmed
Hershko,
Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes.
1987,
Pubmed
Hershko,
The ubiquitin system for protein degradation.
1992,
Pubmed
Hershko,
Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts.
1991,
Pubmed
Hershko,
The protein substrate binding site of the ubiquitin-protein ligase system.
1986,
Pubmed
Hershko,
Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2.
1994,
Pubmed
Holloway,
Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
1993,
Pubmed
Hunt,
The requirements for protein synthesis and degradation, and the control of destruction of cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo.
1992,
Pubmed
Jentsch,
The ubiquitin-conjugation system.
1992,
Pubmed
Lorca,
Cyclin A-cdc2 kinase does not trigger but delays cyclin degradation in interphase extracts of amphibian eggs.
1992,
Pubmed
,
Echinobase
Lorca,
An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs.
1991,
Pubmed
Luca,
Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.
1991,
Pubmed
,
Echinobase
Luca,
Control of programmed cyclin destruction in a cell-free system.
1989,
Pubmed
Mahaffey,
Ubiquitin metabolism in cycling Xenopus egg extracts.
1993,
Pubmed
Mayer,
Detection, resolution, and nomenclature of multiple ubiquitin carboxyl-terminal esterases from bovine calf thymus.
1989,
Pubmed
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
Murray,
Cyclin synthesis drives the early embryonic cell cycle.
1989,
Pubmed
Nishizawa,
Degradation of Mos by the N-terminal proline (Pro2)-dependent ubiquitin pathway on fertilization of Xenopus eggs: possible significance of natural selection for Pro2 in Mos.
1993,
Pubmed
Palombella,
The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B.
1994,
Pubmed
Pickart,
Mechanism of ubiquitin carboxyl-terminal hydrolase. Borohydride and hydroxylamine inactivate in the presence of ubiquitin.
1986,
Pubmed
Reiss,
Specificity of binding of NH2-terminal residue of proteins to ubiquitin-protein ligase. Use of amino acid derivatives to characterize specific binding sites.
1988,
Pubmed
Reiss,
Binding sites of ubiquitin-protein ligase. Binding of ubiquitin-protein conjugates and of ubiquitin-carrier protein.
1989,
Pubmed
Reiss,
Affinity purification of ubiquitin-protein ligase on immobilized protein substrates. Evidence for the existence of separate NH2-terminal binding sites on a single enzyme.
1990,
Pubmed
Scheffner,
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53.
1993,
Pubmed
Schwob,
The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
1994,
Pubmed
Shanklin,
Red light-induced formation of ubiquitin-phytochrome conjugates: Identification of possible intermediates of phytochrome degradation.
1987,
Pubmed
Swenson,
The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.
1986,
Pubmed
Treier,
Ubiquitin-dependent c-Jun degradation in vivo is mediated by the delta domain.
1994,
Pubmed
Westendorf,
The role of cyclin B in meiosis I.
1989,
Pubmed
van der Velden,
Mitotic arrest caused by the amino terminus of Xenopus cyclin B2.
1993,
Pubmed
,
Echinobase
