Scythe regulates apoptosis-inducing factor stability during endoplasmic reticulum stress-induced apoptosis.
Scythe (BAT3; HLA-B associated transcript 3, Bag 6) is a protein that has been implicated in apoptosis because it can modulate the Drosophila melanogaster apoptotic regulator, Reaper. Mice lacking Scythe show pronounced defects in organogenesis and in the regulation of apoptosis and proliferation during mammalian development. However, the biochemical pathways ... important for Scythe function are unknown. We report here multiple levels of interaction between Scythe and the apoptogenic mitochondrial intermembrane protein AIF (apoptosis-inducing factor). Scythe physically interacts with AIF and regulates its stability. AIF stability is markedly reduced in Scythe(-/-) cells, which are more resistant to endoplasmic reticulum stress induced by thapsigargin. Reintroduction of Scythe or overexpression of AIF in Scythe(-/-) cells restores their sensitivity to apoptosis. Together, these data implicate Scythe as a regulator of AIF.
Mesh Terms:
Animals, Apoptosis, Apoptosis Inducing Factor, Carrier Proteins, Cell Differentiation, Cell Line, Cell Proliferation, Drosophila melanogaster, Endoplasmic Reticulum, Gene Expression Regulation, Humans, Mice, Microscopy, Fluorescence, Molecular Chaperones, Nuclear Proteins, Proteins, Transgenes
Animals, Apoptosis, Apoptosis Inducing Factor, Carrier Proteins, Cell Differentiation, Cell Line, Cell Proliferation, Drosophila melanogaster, Endoplasmic Reticulum, Gene Expression Regulation, Humans, Mice, Microscopy, Fluorescence, Molecular Chaperones, Nuclear Proteins, Proteins, Transgenes
J. Biol. Chem.
Date: Feb. 08, 2008
PubMed ID: 18056262
View in: Pubmed Google Scholar
Download Curated Data For This Publication
142655
Switch View:
- Interactions 4