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PMID:15916961

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Citation

Kraft, C, Vodermaier, HC, Maurer-Stroh, S, Eisenhaber, F and Peters, JM (2005) The WD40 propeller domain of Cdh1 functions as a destruction box receptor for APC/C substrates. Mol. Cell 18:543-53

Abstract

Activation of the anaphase-promoting complex/cyclosome (APC/C) by Cdc20 and Cdh1 leads to ubiquitin-dependent degradation of securin and cyclin B and thereby promotes the initiation of anaphase and exit from mitosis. Cyclin B and securin ubiquitination depend on a destruction box (D box) sequence in these proteins, but how APC/C bound to Cdc20 or Cdh1 recognizes the D box is poorly understood. By using site-specific photocrosslinking in combination with mutational analyses, we show that the D box directly interacts with an evolutionarily conserved surface on the predicted WD40 propeller structure of Cdh1 and that this interaction is essential for processive substrate ubiquitination. We further show that Cdh1 specifically crosslinks to the APC/C subunit Cdc27 and that Cdh1 binding to APC/C depends on the presence of Cdc27. Our data imply that APC/C is activated by the association of Cdh1 with Cdc27, which enables APC/C to recognize the D box of substrates via Cdh1's propeller domain.

Links

PubMed Online version:10.1016/j.molcel.2005.04.023

Keywords

Amino Acid Motifs; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/metabolism; Cross-Linking Reagents/chemistry; Cross-Linking Reagents/metabolism; Cyclin B/genetics; Cyclin B/metabolism; DNA Mutational Analysis; Humans; Models, Molecular; Molecular Structure; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Peptides/chemistry; Peptides/genetics; Peptides/metabolism; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Protein Subunits/chemistry; Protein Subunits/genetics; Protein Subunits/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/metabolism; Ubiquitin/metabolism; Ubiquitin-Protein Ligases

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:CDC20

enables

GO:0010997: anaphase-promoting complex binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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