Disease relevance of Birc6

• Remarkably, in addition to being an active ubiquitin-conjugating enzyme, BRUCE bears a baculovirus inhibitor of apoptosis repeat (BIR) motif, which to this date has been exclusively found in apoptosis inhibitors of the IAP-related protein family [1].
• The results suggest that the inhibition of the Bruce effect in LOT-transected females is not due to anosmia induced by the operation procedure, but due to interruption of the primary olfactory bulb projections to the posterior parts of the olfactory cortex [2].
• Although prions are most efficiently propagated via intracerebral inoculation, peripheral administration has caused kuru [Gajdusek et al, 1966], iatrogenic Creutzfeldt-Jakob disease (CJD) [Gibbs et al, 1997], bovine spongiform encephalitis (BSE), and new variant CJD [Hill et al, 1997; Bruce et al, 1997] [3].

Psychiatry related information on Birc6

• Such urinary chemical signals may be involved in pregnancy block (the Bruce effect), aggression, and other mouse social behaviors [4].

High impact information on Birc6

• By using wild-type and mutant forms we show that BRUCE inhibits caspase activity and apoptosis depending on its BIR domain [5].
• Our work suggests that, owing to its two activities and its localization, BRUCE may function as a specialized regulator of cell death pathways [5].
• The Birc6 (Bruce) gene regulates p53 and the mitochondrial pathway of apoptosis and is essential for mouse embryonic development [6].
• In addition, eliminating p53 by RNA interference rescues cell viability induced by Bruce ablation in human cell line H460 [6].
• Here, we show that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality [6].

Biological context of Birc6

• We have generated a mouse line with a mutant allele of the mouse Bruce/Birc6 gene induced by gene trap mutagenesis [7].
• The cause of the Bruce homozygous mutant phenotype is a lack of proliferation of spongiotrophoblast cells in the developing placenta [7].
• In contrast to in vitro data, which indicate a function for Bruce in apoptosis inhibition, the in vivo results presented here suggest instead a role for Bruce in cell division [7].
• Experiments were designed to elucidate the mode of transmission of the male-originating pheromones involved in the induction of estrus (the Whitten effect) and in implantation failure (the Bruce effect) in mice [8].
• Given the proposed key role of the transient receptor potential channel, TRPC2, in VNO signal transduction, we tested whether TRPC2 is essential for memory formation in the context of the Bruce effect [9].

Anatomical context of Birc6

• 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 [10].
• Detection and transduction of pheromonal signals by the mouse vomeronasal organ (VNO) is critical for the formation of a persistent memory required for mate recognition in the context of selective pregnancy failure (the Bruce effect) [9].
• The authors studied anesthetic mutagenesis following exposure in vivo by use of an adaptation of the mouse spermatozoa morphology assay of Wyrobek and Bruce [11].
• The previously studied 'Bruce effect' describes the total loss of preimplantation embryos (pregnancy block) that is apparently caused by the stress induced by the presence of an alien male and mediated by neuroimmunological effects on prolactin activity [12].

Associations of Birc6 with chemical compounds

• The male-induced implantation failure (the Bruce effect) in mice: effect of exogenous progesterone on maintenance of pregnancy in male-exposed females [13].
• Failure of ovo-implantation in newly mated female mice induced by exposure to alien males (Bruce effect) was prevented by administration of 2-(1-piperazinyl) quinoline maleate (quipazine) [14].
• Effect of haloperidol on male-induced implantation failure (Bruce effect) in mice [15].
• Chlorpromazine inhibition of the pheromonal block to pregnancy (the Bruce effect) in mice [16].

Physical interactions of Birc6

• In addition, due to the presence of a C-terminal ubiquitin-conjugating domain, BRUCE can covalently attach ubiquitin to substrates [10].

Other interactions of Birc6

• Complete inactivation of the BRUCE gene resulted in perinatal lethality and growth retardation discernible after embryonic day 14 [10].
• BRUCE is a highly conserved 528-kDa peripheral membrane protein of the trans-Golgi network [10].
• Effect of bilateral transection of the lateral olfactory tract on the male-induced implantation failure (the Bruce effect) in mice [2].
• Since quipazine has serotonin receptor agonistic effect resulting in the elevation of prolactin secretion, it is suggested that the increased secretion of prolactin induced by the drug prevented the Bruce effect [14].

Analytical, diagnostic and therapeutic context of Birc6

• Even though castration abolished the ability of alien males to induce implantation failure (the Bruce effect) in newly inseminated females, treatment of intact alien males with the steroidal antiandrogen, cyproterone acetate, for 14 days (short term) did not significantly depress their ability to induce the Bruce effect [17].
• Failure of adrenalectomy to prevent the male-induced pregnancy block (Bruce effect) in mice [18].

References