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PMID:16628230

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Citation

Kim, HJ, Kim, SH, Shim, SO, Park, E, Kim, C, Kim, K, Tanouye, MA and Yim, J (2007) Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with APPL during Drosophila development. Cell Death Differ. 14:103-15

Abstract

beta-Amyloid precursor protein binding protein 1 (APP-BP1) was previously identified based on its binding to the carboxyl terminal of beta-amyloid precursor protein. In this report, we have discovered that a mutation of dAPP-BP1 (Drosophila ortholog of APP-BP1) hinders tissue development, causes apoptosis in imaginal disc cells, and blocks the NEDD8 conjugation pathway. We show that dAPP-BP1 specifically binds the intracellular domain of APP-like protein (APPL). The dAPP-BP1 mutation partially suppresses the abnormal macrochaete phenotype of Appl(d), while overexpression of dAPP-BP1 causes abnormal macrochaetes. When APPL is overexpressed, the normal bristle pattern in the fly thorax is disturbed and apoptosis is induced in wing imaginal discs. APPL overexpression phenotypes are enhanced by reducing the level of dAPP-BP1. APPL overexpression is shown to inhibit the NEDD8 conjugation pathway. APPL-induced apoptosis is rescued by overexpression of dAPP-BP1. Our data suggest that APPL and dAPP-BP1 interact antagonistically during Drosophila development.

Links

PubMed Online version:10.1038/sj.cdd.4401935

Keywords

Amino Acid Sequence; Animals; Apoptosis; Cell Proliferation; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Drosophila/embryology; Drosophila/growth & development; Drosophila/metabolism; Drosophila Proteins/antagonists & inhibitors; Drosophila Proteins/chemistry; Drosophila Proteins/metabolism; Membrane Proteins/antagonists & inhibitors; Membrane Proteins/chemistry; Membrane Proteins/metabolism; Molecular Sequence Data; Mutation; Nerve Tissue Proteins/antagonists & inhibitors; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/metabolism; Phenotype; SKP Cullin F-Box Protein Ligases/metabolism; Sequence Alignment; Thorax/embryology; Thorax/metabolism; Ubiquitins/metabolism

Significance

Annotations

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

DROME:A4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0261112

F

Seeded From UniProt

complete

DROME:A4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9VTE9

F

Seeded From UniProt

complete

DROME:ULA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0000108

F

Seeded From UniProt

complete

DROME:ULA1

contributes_to

GO:0019781: NEDD8 activating enzyme activity

ECO:0000250: sequence similarity evidence used in manual assertion

HGNC:621

F

Seeded From UniProt

complete

DROME:ULA1

involved_in

GO:0045116: protein neddylation

ECO:0000250: sequence similarity evidence used in manual assertion

HGNC:621

P

Seeded From UniProt

complete

DROME:ULA1

involved_in

GO:0045116: protein neddylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:ULA1

enables

GO:0001540: amyloid-beta binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P14599

F

Seeded From UniProt

complete


See also

References

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