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Genes Dev
2000 Sep 15;1418:2344-57. doi: 10.1101/gad.823200.
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A nonproteolytic function of the proteasome is required for the dissociation of Cdc2 and cyclin B at the end of M phase.
Nishiyama A
,
Tachibana K
,
Igarashi Y
,
Yasuda H
,
Tanahashi N
,
Tanaka K
,
Ohsumi K
,
Kishimoto T
.
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Inactivation of cyclin B-Cdc2 kinase at the exit from M phase depends on the specific proteolysis of the cyclin B subunit, whereas the Cdc2 subunit remains present at nearly constant levels throughout the cell cycle. It is unknown how Cdc2 escapes degradation when cyclin B is destroyed. In Xenopus egg extracts that reproduce the exit from M phase in vitro, we have found that dissociation of the cyclin B-Cdc2 complex occurred under conditions where cyclin B was tethered to the 26S proteasome but not yet degraded. The dephosphorylation of Thr 161 on Cdc2 was unlikely to be necessary for the dissociation of the two subunits. However, the dissociation was dependent on the presence of a functional destruction box in cyclin B. Cyclin B ubiquitination was also, by itself, not sufficient for separation of Cdc2 and cyclin B. The 26S proteasome, but not the 20S proteasome, was capable of dissociating the two subunits. These results indicate that the cyclin B and Cdc2 subunits are separated by the proteasome through a mechanism that precedes proteolysis of cyclin B and is independent of proteolysis. As a result, cyclin B levels decrease on exit from M phase but Cdc2 levels remain constant.
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10995390
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Baumeister,
The proteasome: paradigm of a self-compartmentalizing protease.
1998, Pubmed
Baumeister,
The proteasome: paradigm of a self-compartmentalizing protease.
1998,
Pubmed
Braun,
The base of the proteasome regulatory particle exhibits chaperone-like activity.
1999,
Pubmed
Cohen-Fix,
Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit.
1999,
Pubmed
Confalonieri,
A 200-amino acid ATPase module in search of a basic function.
1995,
Pubmed
Dai,
Involvement of valosin-containing protein, an ATPase Co-purified with IkappaBalpha and 26 S proteasome, in ubiquitin-proteasome-mediated degradation of IkappaBalpha.
1998,
Pubmed
Deveraux,
Inhibition of ubiquitin-mediated proteolysis by the Arabidopsis 26 S protease subunit S5a.
1995,
Pubmed
,
Xenbase
Deveraux,
A 26 S protease subunit that binds ubiquitin conjugates.
1994,
Pubmed
Dunphy,
The Xenopus cdc2 protein is a component of MPF, a cytoplasmic regulator of mitosis.
1988,
Pubmed
,
Xenbase
Fesquet,
The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues.
1993,
Pubmed
,
Xenbase
Funabiki,
Fission yeast Cut2 required for anaphase has two destruction boxes.
1997,
Pubmed
,
Xenbase
Genschik,
Cell cycle -dependent proteolysis in plants. Identification Of the destruction box pathway and metaphase arrest produced by the proteasome inhibitor mg132.
1998,
Pubmed
Ghosh,
NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.
1998,
Pubmed
Glickman,
A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3.
1998,
Pubmed
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Hershko,
The ubiquitin system.
1998,
Pubmed
Hershko,
Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2.
1994,
Pubmed
Kaiser,
Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets.
1999,
Pubmed
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
King,
How proteolysis drives the cell cycle.
1996,
Pubmed
Kobayashi,
Identification of the domains in cyclin A required for binding to, and activation of, p34cdc2 and p32cdk2 protein kinase subunits.
1992,
Pubmed
,
Xenbase
Koepp,
How the cyclin became a cyclin: regulated proteolysis in the cell cycle.
1999,
Pubmed
Kominami,
Yeast counterparts of subunits S5a and p58 (S3) of the human 26S proteasome are encoded by two multicopy suppressors of nin1-1.
1997,
Pubmed
Kotani,
Regulation of APC activity by phosphorylation and regulatory factors.
1999,
Pubmed
Lees,
Sequences within the conserved cyclin box of human cyclin A are sufficient for binding to and activation of cdc2 kinase.
1993,
Pubmed
,
Xenbase
Lorca,
Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
1992,
Pubmed
,
Xenbase
Mahaffey,
Ubiquitin metabolism in cycling Xenopus egg extracts.
1993,
Pubmed
,
Xenbase
Maniatis,
A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways.
1999,
Pubmed
Morgan,
Regulation of the APC and the exit from mitosis.
1999,
Pubmed
Morgan,
Principles of CDK regulation.
1995,
Pubmed
Murakami,
Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination.
1992,
Pubmed
Murakami,
ATP-Dependent inactivation and sequestration of ornithine decarboxylase by the 26S proteasome are prerequisites for degradation.
1999,
Pubmed
Murray,
Dominoes and clocks: the union of two views of the cell cycle.
1989,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Nasmyth,
Splitting the chromosome: cutting the ties that bind sister chromatids.
2000,
Pubmed
Nigg,
Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle.
1995,
Pubmed
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Okumura,
Initial triggering of M-phase in starfish oocytes: a possible novel component of maturation-promoting factor besides cdc2 kinase.
1996,
Pubmed
Pickart,
Targeting of substrates to the 26S proteasome.
1997,
Pubmed
Prinz,
Dual control of mitotic exit.
1999,
Pubmed
Rock,
Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.
1994,
Pubmed
Russell,
The 19S regulatory complex of the proteasome functions independently of proteolysis in nucleotide excision repair.
1999,
Pubmed
Sherwood,
In vivo inhibition of cyclin B degradation and induction of cell-cycle arrest in mammalian cells by the neutral cysteine protease inhibitor N-acetylleucylleucylnorleucinal.
1993,
Pubmed
Shirayama,
APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5.
1999,
Pubmed
Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed
Tanahashi,
Chromosomal localization and immunological analysis of a family of human 26S proteasomal ATPases.
1998,
Pubmed
Tanaka,
Proteasomes (multi-protease complexes) as 20 S ring-shaped particles in a variety of eukaryotic cells.
1988,
Pubmed
,
Xenbase
Thrower,
Recognition of the polyubiquitin proteolytic signal.
2000,
Pubmed
Tinker-Kulberg,
Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage.
1999,
Pubmed
Towbin,
Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
1979,
Pubmed
Townsley,
Proteolytic ratchets that control progression through mitosis.
1998,
Pubmed
Young,
Characterization of two polyubiquitin binding sites in the 26 S protease subunit 5a.
1998,
Pubmed
Zachariae,
Whose end is destruction: cell division and the anaphase-promoting complex.
1999,
Pubmed
Zou,
Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis.
1999,
Pubmed
,
Xenbase
