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PMID:19129189

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Citation

Temme, C, Weissbach, R, Lilie, H, Wilson, C, Meinhart, A, Meyer, S, Golbik, R, Schierhorn, A and Wahle, E (2009) The Drosophila melanogaster Gene cg4930 Encodes a High Affinity Inhibitor for Endonuclease G. J. Biol. Chem. 284:8337-48

Abstract

Endonuclease G (EndoG) is a mitochondrial enzyme believed to be released during apoptosis to participate in the degradation of nuclear DNA. This paper describes a Drosophila protein, EndoGI, which inhibits EndoG specifically. EndoG and EndoGI associate with subpicomolar affinity, forming a 2:1 complex in which dimeric EndoG is bound by two tandemly repeated homologous domains of monomeric EndoGI. Binding appears to involve the active site of EndoG. EndoGI is present in the cell nucleus at micromolar concentrations. Upon induction of apoptosis, levels of the inhibitor appear to be reduced, and it is relocalized to the cytoplasm. EndoGI, encoded by the predicted open reading frame cg4930, is expressed throughout Drosophila development. Flies homozygous for a hypomorphic EndoGI mutation have a strongly reduced viability, which is modulated by genetic background and diet. We propose that EndoGI protects the cell against low levels of EndoG outside mitochondria.

Links

PubMed PMC2659192 Online version:10.1074/jbc.M808319200

Keywords

Animals; Cell Line; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster; Endodeoxyribonucleases/antagonists & inhibitors; Endodeoxyribonucleases/genetics; Endodeoxyribonucleases/metabolism; Enzyme Inhibitors/metabolism; Mitochondria/genetics; Mitochondria/metabolism; Protein Binding/physiology; Protein Structure, Tertiary/physiology

Significance

Annotations

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

DROME:Q7JXB9

enables

GO:0004520: endodeoxyribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q7JXB9

enables

GO:0004521: endoribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9V3V9

enables

GO:0008428: ribonuclease inhibitor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9V3V9

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q9V3V9

involved_in

GO:0060702: negative regulation of endoribonuclease activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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