title: The reaper-binding protein scythe modulates apoptosis and proliferation during mammalian development.
abstract: Scythe (BAT3 [HLA-B-associated transcript 3]) is a nuclear protein that has been implicated in apoptosis, as it can modulate Reaper, a central apoptotic regulator in Drosophila melanogaster. While Scythe can markedly affect Reaper-dependent apoptosis in Xenopus laevis cell extracts, the function of Scythe in mammals is unknown. Here, we report that inactivation of Scythe in the mouse results in lethality associated with pronounced developmental defects in the lung, kidney, and brain. In all cases, these developmental defects were associated with dysregulation of apoptosis and cellular proliferation. Scythe-/- cells were also more resistant to apoptosis induced by menadione and thapsigargin. These data show that Scythe is critical for viability and normal development, probably via regulation of programmed cell death and cellular proliferation.
authors.affiliation: St. Jude Children's Research Hospital, Department of Genetics and Tumor Cell Biology, 332N Lauderdale, Memphis, TN 38105, USA.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Desmots
authors.forename: Helen R
authors.initials: HR
authors.lastname: Russell
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Lee
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McKinnon
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000002:abnormalities / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008168:Lung / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: C484266:Bag6 protein, mouse; D002352:Carrier Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins