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Mol Cell Biol
2003 May 01;2310:3497-505. doi: 10.1128/MCB.23.10.3497-3505.2003.
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Two ubiquitin-conjugating enzymes, UbcP1/Ubc4 and UbcP4/Ubc11, have distinct functions for ubiquitination of mitotic cyclin.
Seino H
,
Kishi T
,
Nishitani H
,
Yamao F
.
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Cell cycle events are regulated by sequential activation and inactivation of Cdk kinases. Mitotic exit is accomplished by the inactivation of mitotic Cdk kinase, which is mainly achieved by degradation of cyclins. The ubiquitin-proteasome system is involved in this process, requiring APC/C (anaphase-promoting complex/cyclosome) as a ubiquitin ligase. In Xenopus and clam oocytes, the ubiquitin-conjugating enzymes that function with APC/C have been identified as two proteins, UBC4 and UBCx/E2-C. Previously we reported that the fission yeast ubiquitin-conjugating enzyme UbcP4/Ubc11, a homologue of UBCx/E2-C, is required for mitotic transition. Here we show that the other fission yeast ubiquitin-conjugating enzyme, UbcP1/Ubc4, which is homologous to UBC4, is also required for mitotic transition in the same manner as UbcP4/Ubc11. Both ubiquitin-conjugating enzymes are essential for cell division and directly required for the degradation of mitotic cyclin Cdc13. They function nonredundantly in the ubiquitination of CDC13 because a defect in ubcP1/ubc4+ cannot be suppressed by high expression of UbcP4/Ubc11 and a defect in ubcP4/ubc11+ cannot be suppressed by high expression of UbcP1/Ubc4. In vivo analysis of the ubiquitinated state of Cdc13 shows that the ubiquitin chains on Cdc13 were short in ubcP1/ubc4 mutant cells while ubiquitinated Cdc13 was totally reduced in ubcP4/ubc11 mutant cells. Taken together, these results indicate that the two ubiquitin-conjugating enzymes play distinct and essential roles in the degradation of mitotic cyclin Cdc13, with the UbcP4/Ubc11-pathway initiating ubiquitination of Cdc13 and the UbcP1/Ubc4-pathway elongating the short ubiquitin chains on Cdc13.
Aristarkhov,
E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins.
1996, Pubmed
Aristarkhov,
E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins.
1996,
Pubmed
Bastians,
Cell cycle-regulated proteolysis of mitotic target proteins.
1999,
Pubmed
,
Xenbase
Blanco,
APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited by cdc2 phosphorylation.
2000,
Pubmed
Broek,
Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.
1991,
Pubmed
Ciechanover,
The ubiquitin-proteasome pathway: on protein death and cell life.
1998,
Pubmed
Ciechanover,
Ubiquitin-mediated proteolysis: biological regulation via destruction.
2000,
Pubmed
Ellison,
A site-directed approach for constructing temperature-sensitive ubiquitin-conjugating enzymes reveals a cell cycle function and growth function for RAD6.
1991,
Pubmed
Fujimuro,
Production and characterization of monoclonal antibodies specific to multi-ubiquitin chains of polyubiquitinated proteins.
1994,
Pubmed
Gmachl,
The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex.
2000,
Pubmed
Gordon,
Defective mitosis due to a mutation in the gene for a fission yeast 26S protease subunit.
1993,
Pubmed
Hayles,
Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34cdc2-mitotic B cyclin complex.
1994,
Pubmed
Hershko,
Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2.
1994,
Pubmed
Hilioti,
The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner.
2001,
Pubmed
Iacovoni,
A new inducible protein expression system in fission yeast based on the glucose-repressed inv1 promoter.
1999,
Pubmed
Irniger,
Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast.
1995,
Pubmed
Javerzat,
Fission yeast genes which disrupt mitotic chromosome segregation when overexpressed.
1996,
Pubmed
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
Kitamura,
Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative regulator of cell cycle progression during G1-phase.
1998,
Pubmed
Kominami,
Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast.
1998,
Pubmed
Kramer,
Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family.
1998,
Pubmed
,
Xenbase
Leverson,
The APC11 RING-H2 finger mediates E2-dependent ubiquitination.
2000,
Pubmed
Luca,
Control of programmed cyclin destruction in a cell-free system.
1989,
Pubmed
Matsumoto,
A fission yeast homolog of CDC20/p55CDC/Fizzy is required for recovery from DNA damage and genetically interacts with p34cdc2.
1997,
Pubmed
Maundrell,
Thiamine-repressible expression vectors pREP and pRIP for fission yeast.
1993,
Pubmed
Mitsuzawa,
Two WD repeat-containing TATA-binding protein-associated factors in fission yeast that suppress defects in the anaphase-promoting complex.
2001,
Pubmed
Murray,
Cyclin ubiquitination: the destructive end of mitosis.
1995,
Pubmed
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase
Nurse,
Universal control mechanism regulating onset of M-phase.
1990,
Pubmed
Nurse,
Ordering S phase and M phase in the cell cycle.
1994,
Pubmed
Osaka,
A ubiquitin-conjugating enzyme in fission yeast that is essential for the onset of anaphase in mitosis.
1997,
Pubmed
Samejima,
Bypassing anaphase by fission yeast cut9 mutation: requirement of cut9+ to initiate anaphase.
1994,
Pubmed
Schwab,
Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
1997,
Pubmed
Schwab,
Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC.
2001,
Pubmed
Sigrist,
Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles.
1997,
Pubmed
,
Xenbase
Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed
Sánchez-Díaz,
The Cdk inhibitors p25rum1 and p40SIC1 are functional homologues that play similar roles in the regulation of the cell cycle in fission and budding yeast.
1998,
Pubmed
Tang,
APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.
2001,
Pubmed
Townsley,
Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase.
1997,
Pubmed
Townsley,
Functional analysis of the Saccharomyces cerevisiae UBC11 gene.
1998,
Pubmed
Tugendreich,
CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition.
1995,
Pubmed
Varshavsky,
The ubiquitin system.
1997,
Pubmed
Visintin,
CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
1997,
Pubmed
Yamaguchi,
A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes.
1997,
Pubmed
Yamaguchi,
Fission yeast Fizzy-related protein srw1p is a G(1)-specific promoter of mitotic cyclin B degradation.
2000,
Pubmed
Yamano,
The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe.
1996,
Pubmed
,
Xenbase
Yanagida,
Cell cycle mechanisms of sister chromatid separation; roles of Cut1/separin and Cut2/securin.
2000,
Pubmed
Yu,
Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation.
1996,
Pubmed
,
Xenbase
Zachariae,
Whose end is destruction: cell division and the anaphase-promoting complex.
1999,
Pubmed
Zhang,
Ubiquitin-dependent degradation of cyclin B is accelerated in polyploid megakaryocytes.
1998,
Pubmed
