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PMID:12021769

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Citation

Ryoo, HD, Bergmann, A, Gonen, H, Ciechanover, A and Steller, H (2002) Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. Nat. Cell Biol. 4:432-8

Abstract

Cell death in higher organisms is negatively regulated by Inhibitor of Apoptosis Proteins (IAPs), which contain a ubiquitin ligase motif, but how ubiquitin-mediated protein degradation is regulated during apoptosis is poorly understood. Here, we report that Drosophila melanogaster IAP1 (DIAP1) auto-ubiquitination and degradation is actively regulated by Reaper (Rpr) and UBCD1. We show that Rpr, but not Hid (head involution defective), promotes significant DIAP1 degradation. Rpr-mediated DIAP1 degradation requires an intact DIAP1 RING domain. Among the mutations affecting ubiquitination, we found ubcD1, which suppresses rpr-induced apoptosis. UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation.

Links

PubMed Online version:10.1038/ncb795

Keywords

Age Factors; Animals; Apoptosis/physiology; Caspases/metabolism; Cell Count; Drosophila Proteins/chemistry; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Gene Expression Regulation, Developmental; Inhibitor of Apoptosis Proteins; Ligases/genetics; Ligases/metabolism; Mutagenesis/physiology; Neurons, Afferent/cytology; Neuropeptides/genetics; Neuropeptides/metabolism; Peptides/genetics; Peptides/metabolism; Protein Binding/physiology; Protein Structure, Tertiary; RNA Processing, Post-Transcriptional/physiology; Ubiquitin/metabolism; Ubiquitin-Conjugating Enzymes

Significance

Annotations

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

DROME:UBCD1

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0260635

F

Seeded From UniProt

complete

DROME:UBCD1

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:UBCD1

enables

GO:0061631: ubiquitin conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:HID

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24306

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0003997

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011706

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011217

F

Seeded From UniProt

complete

DROME:DIAP1

involved_in

GO:0051865: protein autoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24106

F

Seeded From UniProt

complete

DROME:DIAP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24475

F

Seeded From UniProt

complete

DROME:RPR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q24306

F

Seeded From UniProt

complete

DROME:HID

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0260635

F

Seeded From UniProt

complete

DROME:IAP1

involved_in

GO:0051865: protein autoubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:IAP1

enables

GO:0031624: ubiquitin conjugating enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0011217

F

Seeded From UniProt

complete

DROME:IAP1

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:RPR

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0260635

F

Seeded From UniProt

complete

DROME:RPR

involved_in

GO:0031398: positive regulation of protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RPR

involved_in

GO:2000060: positive regulation of ubiquitin-dependent protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

FB:FBgn0011217

P

Seeded From UniProt

complete


See also

References

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