Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Listovsky T
,
Oren YS
,
Yudkovsky Y
,
Mahbubani HM
,
Weiss AM
,
Lebendiker M
,
Brandeis M
.
???displayArticle.abstract???
The Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase mediates degradation of cell cycle proteins during mitosis and G1. Cdc20/Fzy and Cdh1/Fzr are substrate-specific APC/C activators. The level of mammalian Cdh1 is high in mitosis, but it is inactive and does not bind the APC/C. We show that when Cdh1 is active in G1 and G0, its levels are considerably lower and almost all of it is APC/C associated. We demonstrate that Cdh1 is subject to APC/C-specific degradation in G1 and G0, and that this degradation depends upon two RXXL-type destruction boxes. We further demonstrate that addition of Cdh1 to Xenopus interphase extracts, which have an inactive APC/C, activates it to degrade Cdh1. These observations indicate that Cdh1 mediates its own degradation by activating the APC/C to degrade itself. Elevated levels of Cdh1 are deleterious for cell cycle progression in various organisms. This auto-regulation of Cdh1 could thus play a role in ensuring that the level of Cdh1 is reduced during G1 and G0, allowing it to be switched off at the correct time.
Brandeis,
The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.
1996, Pubmed
Brandeis,
The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.
1996,
Pubmed
Burton,
D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p.
2001,
Pubmed
Chen,
MAD2B is an inhibitor of the anaphase-promoting complex.
2001,
Pubmed
,
Xenbase
Fang,
The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation.
1998,
Pubmed
,
Xenbase
Golan,
The cyclin-ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1-cyclin B and Plk.
2002,
Pubmed
Hagting,
Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1.
2002,
Pubmed
Harper,
A phosphorylation-driven ubiquitination switch for cell-cycle control.
2002,
Pubmed
Hilioti,
The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner.
2001,
Pubmed
Holloway,
Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
1993,
Pubmed
,
Xenbase
Hsu,
E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1).
2002,
Pubmed
,
Xenbase
Inbal,
The mammalian Fizzy and Fizzy-related genes are regulated at the transcriptional and post-transcriptional levels.
1999,
Pubmed
Jacobs,
A complex degradation signal in Cyclin A required for G1 arrest, and a C-terminal region for mitosis.
2001,
Pubmed
King,
A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.
1995,
Pubmed
,
Xenbase
Kraft,
Mitotic regulation of the human anaphase-promoting complex by phosphorylation.
2003,
Pubmed
Kramer,
Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family.
1998,
Pubmed
,
Xenbase
Kramer,
Mitotic regulation of the APC activator proteins CDC20 and CDH1.
2000,
Pubmed
,
Xenbase
Leismann,
Drosophila securin destruction involves a D-box and a KEN-box and promotes anaphase in parallel with Cyclin A degradation.
2003,
Pubmed
Listovsky,
Cdk1 is essential for mammalian cyclosome/APC regulation.
2000,
Pubmed
Lorca,
Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
Lukas,
Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex.
1999,
Pubmed
Murray,
Cell cycle extracts.
1991,
Pubmed
Peters,
The anaphase-promoting complex: proteolysis in mitosis and beyond.
2002,
Pubmed
Pfleger,
Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1.
2001,
Pubmed
,
Xenbase
Pfleger,
Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex.
2001,
Pubmed
,
Xenbase
Pfleger,
The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1.
2000,
Pubmed
,
Xenbase
Reimann,
Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex.
2001,
Pubmed
,
Xenbase
Rudner,
Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex.
2000,
Pubmed
Schwab,
Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC.
2001,
Pubmed
Schwab,
Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
1997,
Pubmed
Shirayama,
The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae.
1998,
Pubmed
Shteinberg,
Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20.
1999,
Pubmed
Sigrist,
Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3.
1995,
Pubmed
Sigrist,
Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles.
1997,
Pubmed
,
Xenbase
Sorensen,
Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.
2000,
Pubmed
Stemmann,
Dual inhibition of sister chromatid separation at metaphase.
2001,
Pubmed
,
Xenbase
Sudakin,
Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2.
2001,
Pubmed
Sudakin,
The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
1995,
Pubmed
Tang,
Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1.
2001,
Pubmed
,
Xenbase
Visintin,
CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
1997,
Pubmed
Vodermaier,
TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1.
2003,
Pubmed
Wheatley,
CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo.
1997,
Pubmed
Wirbelauer,
The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts.
2000,
Pubmed
Yamanaka,
Cell cycle-dependent expression of mammalian E2-C regulated by the anaphase-promoting complex/cyclosome.
2000,
Pubmed
Yamano,
Cell cycle-regulated recognition of the destruction box of cyclin B by the APC/C in Xenopus egg extracts.
2004,
Pubmed
,
Xenbase
Yamano,
The role of the destruction box and its neighbouring lysine residues in cyclin B for anaphase ubiquitin-dependent proteolysis in fission yeast: defining the D-box receptor.
1998,
Pubmed
Yudkovsky,
Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint.
2000,
Pubmed
Zachariae,
Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex.
1998,
Pubmed
Zur,
Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes.
2002,
Pubmed
Zur,
Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis.
2001,
Pubmed
