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PMID:15485903

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Citation

Lotz, K, Pyrowolakis, G and Jentsch, S (2004) BRUCE, a giant E2/E3 ubiquitin ligase and inhibitor of apoptosis protein of the trans-Golgi network, is required for normal placenta development and mouse survival. Mol. Cell. Biol. 24:9339-50

Abstract

BRUCE is a highly conserved 528-kDa peripheral membrane protein of the trans-Golgi network. Owing to the presence of an N-terminal single baculovirus inhibitor repeat, BRUCE functions as an inhibitor of apoptosis protein and blocks apoptosis when overexpressed. In addition, due to the presence of a C-terminal ubiquitin-conjugating domain, BRUCE can covalently attach ubiquitin to substrates. Here we report the generation and characterization of BRUCE-deficient mice. Complete inactivation of the BRUCE gene resulted in perinatal lethality and growth retardation discernible after embryonic day 14. The growth defect is linked to impaired placental development and may be caused by insufficient oxygen and nutrient transfer across the placenta. Chorioallantoic placentation initiated normally, but the mutant placenta showed an impaired maturation of the labyrinth layer and a significant reduction of the spongiotrophoblast. No evidence for an elevated apoptosis rate was detectable in embryonic and extraembryonic tissues and in knockout fibroblasts. Thus, although BRUCE is broadly expressed in embryonic, extraembryonic, and adult mouse tissues, this bifunctional protein might play a unique role in normal trophoblast differentiation and embryonic survival.

Links

PubMed PMC522247 Online version:10.1128/MCB.24.21.9339-9350.2004

Keywords

Animals; Apoptosis; Cell Division; Cells, Cultured; Embryo, Mammalian/cytology; Embryo, Mammalian/embryology; Embryo, Mammalian/metabolism; Female; Fibroblasts; Gene Deletion; Genes, Essential/genetics; Genotype; In Situ Hybridization; Inhibitor of Apoptosis Proteins; Mice; Mice, Knockout; Neoplasm Proteins/deficiency; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Placenta/cytology; Placenta/growth & development; Placenta/metabolism; Pregnancy; RNA, Messenger/analysis; RNA, Messenger/genetics; Ubiquitin-Protein Ligases/deficiency; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism; trans-Golgi Network/metabolism

Significance

Annotations

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

MOUSE:BIRC6

involved_in

GO:0001890: placenta development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BIRC6

acts_upstream_of_or_within

GO:0060712: spongiotrophoblast layer development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3512417

P

  • results_in_development_of:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:BIRC6

acts_upstream_of_or_within

GO:0060711: labyrinthine layer development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3512417

P

  • results_in_development_of:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:BIRC6

acts_upstream_of_or_within

GO:0042127: regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3512417

P

  • occurs_in:(EMAPA:16042)|occurs_in:(EMAPA:16042)

Seeded From UniProt

complete


See also

References

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