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.
???displayArticle.abstract???
The specificity of ubiquitin-mediated protein degradation with regards to the selection of substrates to be polyubiquitinated has only been determined rather recently. Substrate targeting by the N-end rule and HECT (homology to E6AP carboxyl terminus) domain ubiquitin ligases occurs through substrate-specific binding domains. In contrast, the SCF complex recruits substrates through a substrate adaptor protein, the F-box subunit. Despite evidence showing that Cdc20 and Cdh1 bind and activate the anaphase-promoting complex (APC) in a substrate-specific manner, there is no evidence that the activating protein and substrate interact directly; hence, no clear model exists for the mechanism of APC activation or recruitment of substrates. We show here that the activators Cdc20 and Cdh1 can associate with substrates via their N termini. In the absence of APC, Cdc20 and Cdh1 bind substrates reflecting Cdc20-APC and Cdh1-APC specificity. The N termini of Cdc20 and Cdh1 provide specificity functionally, as demonstrated by the generation of active chimeras that display the specificity corresponding to their N termini. Thus, Cdc20 and Cdh1 act as both substrate recognition and activating modules for APC.
???displayArticle.pubmedLink???
11562349 ???displayArticle.pmcLink???PMC312782 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Agami,
Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage.
2000, Pubmed
Agami,
Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage.
2000,
Pubmed Bai,
SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
1996,
Pubmed Bartel,
The recognition component of the N-end rule pathway.
1990,
Pubmed Baumeister,
The proteasome: paradigm of a self-compartmentalizing protease.
1998,
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 Burton,
Hsl1p, a Swe1p inhibitor, is degraded via the anaphase-promoting complex.
2000,
Pubmed Cohen-Fix,
Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p.
1996,
Pubmed
,
Xenbase Coux,
Structure and functions of the 20S and 26S proteasomes.
1996,
Pubmed 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 Fang,
Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.
1998,
Pubmed
,
Xenbase Funabiki,
The Xenopus chromokinesin Xkid is essential for metaphase chromosome alignment and must be degraded to allow anaphase chromosome movement.
2000,
Pubmed
,
Xenbase Funabiki,
Cut2 proteolysis required for sister-chromatid seperation in fission yeast.
1996,
Pubmed Gieffers,
Three-dimensional structure of the anaphase-promoting complex.
2001,
Pubmed Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase Gmachl,
The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex.
2000,
Pubmed Gonda,
Universality and structure of the N-end rule.
1989,
Pubmed Hein,
NPl1, an essential yeast gene involved in induced degradation of Gap1 and Fur4 permeases, encodes the Rsp5 ubiquitin-protein ligase.
1995,
Pubmed Hershko,
The ubiquitin system.
1998,
Pubmed Holloway,
Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor.
1993,
Pubmed
,
Xenbase Hsiung,
F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat.
2001,
Pubmed Irniger,
The anaphase-promoting complex is required in G1 arrested yeast cells to inhibit B-type cyclin accumulation and to prevent uncontrolled entry into S-phase.
1997,
Pubmed Jackson,
The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases.
2000,
Pubmed Kamura,
Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.
1999,
Pubmed Kawahara,
Inhibiting proteasome activity causes overreplication of DNA and blocks entry into mitosis in sea urchin embryos.
2000,
Pubmed King,
Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates.
1996,
Pubmed
,
Xenbase Kishi,
An essential function of Grr1 for the degradation of Cln2 is to act as a binding core that links Cln2 to Skp1.
1998,
Pubmed Kramer,
Mitotic regulation of the APC activator proteins CDC20 and CDH1.
2000,
Pubmed
,
Xenbase Kumar,
Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination.
1999,
Pubmed McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase Murray,
Cell cycle extracts.
1991,
Pubmed Nefsky,
Pub1 acts as an E6-AP-like protein ubiquitiin ligase in the degradation of cdc25.
1996,
Pubmed Oda,
Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination.
1999,
Pubmed Ohtoshi,
Human p55(CDC)/Cdc20 associates with cyclin A and is phosphorylated by the cyclin A-Cdk2 complex.
2000,
Pubmed Peters,
SCF and APC: the Yin and Yang of cell cycle regulated proteolysis.
1998,
Pubmed Pfleger,
Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1.
2001,
Pubmed
,
Xenbase Pfleger,
The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1.
2000,
Pubmed
,
Xenbase 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 Rotin,
WW (WWP) domains: from structure to function.
1998,
Pubmed Schwab,
Yeast Hct1 is a regulator of Clb2 cyclin proteolysis.
1997,
Pubmed Seol,
Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34.
1999,
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 Sorensen,
Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.
2000,
Pubmed Sørensen,
A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression.
2001,
Pubmed Tyers,
Proteolysis and the cell cycle: with this RING I do thee destroy.
2000,
Pubmed Utrera,
A novel p53-inducible gene coding for a microtubule-localized protein with G2-phase-specific expression.
1998,
Pubmed Varshavsky,
The N-end rule: functions, mysteries, uses.
1996,
Pubmed Visintin,
CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis.
1997,
Pubmed Wang,
Functional domains of the Rsp5 ubiquitin-protein ligase.
1999,
Pubmed Yamamoto,
Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s).
1996,
Pubmed Yeh,
The F-box protein SKP2 binds to the phosphorylated threonine 380 in cyclin E and regulates ubiquitin-dependent degradation of cyclin E.
2001,
Pubmed 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 Zachariae,
Whose end is destruction: cell division and the anaphase-promoting complex.
1999,
Pubmed Zhang,
Identification of an overlapping binding domain on Cdc20 for Mad2 and anaphase-promoting complex: model for spindle checkpoint regulation.
2001,
Pubmed Zhu,
A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation.
1999,
Pubmed
,
Xenbase Zou,
Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis.
1999,
Pubmed
,
Xenbase
