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PMID:19822757

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Citation

Williamson, A, Wickliffe, KE, Mellone, BG, Song, L, Karpen, GH and Rape, M (2009) Identification of a physiological E2 module for the human anaphase-promoting complex. Proc. Natl. Acad. Sci. U.S.A. 106:18213-8

Abstract

Ubiquitination by the anaphase-promoting complex (APC/C) is essential for proliferation in all eukaryotes. The human APC/C promotes the degradation of mitotic regulators by assembling K11-linked ubiquitin chains, the formation of which is initiated by its E2 UbcH10. Here, we identify the conserved Ube2S as a K11-specific chain elongating E2 for human and Drosophila APC/C. Ube2S depends on the cell cycle-dependent association with the APC/C activators Cdc20 and Cdh1 for its activity. While depletion of Ube2S already inhibits APC/C in cells, the loss of the complete UbcH10/Ube2S-module leads to dramatic stabilization of APC/C substrates, severe spindle defects, and a strong mitotic delay. Ube2S and UbcH10 are tightly co-regulated in the cell cycle by APC/C-dependent degradation. We conclude that UbcH10 and Ube2S constitute a physiological E2-module for APC/C, the activity of which is required for spindle assembly and cell division.

Links

PubMed PMC2775311 Online version:10.1073/pnas.0907887106

Keywords

Animals; Biocatalysis; Drosophila melanogaster/metabolism; HeLa Cells; Humans; Mitosis; Protein Binding; Ubiquitin/metabolism; Ubiquitin-Conjugating Enzymes/genetics; Ubiquitin-Conjugating Enzymes/metabolism; Ubiquitin-Protein Ligase Complexes/metabolism

Significance

Annotations

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

HUMAN:UBE2C

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P12830

F

Seeded From UniProt

complete

HUMAN:UBE2C

involved_in

GO:0031145: anaphase-promoting complex-dependent catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2C

involved_in

GO:0010994: free ubiquitin chain polymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2C

involved_in

GO:0010458: exit from mitosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2C

contributes_to

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBE2C

involved_in

GO:0070979: protein K11-linked ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2C

part_of

GO:0005680: anaphase-promoting complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CADH1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00762

F

Seeded From UniProt

complete

HUMAN:UBE2S

involved_in

GO:0031145: anaphase-promoting complex-dependent catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2S

involved_in

GO:0010994: free ubiquitin chain polymerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2S

involved_in

GO:0010458: exit from mitosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2S

part_of

GO:0005680: anaphase-promoting complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:UBE2S

contributes_to

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:UBE2S

involved_in

GO:0070979: protein K11-linked ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:UBE2S

involved_in

GO:1904668: positive regulation of ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBE2C

involved_in

GO:0031145: anaphase-promoting complex-dependent catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBE2C

involved_in

GO:0010458: exit from mitosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBE2S

involved_in

GO:0031145: anaphase-promoting complex-dependent catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBE2S

involved_in

GO:0010458: exit from mitosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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