title: Augmentation of drug-induced cell death by ER protein BRI3BP.
abstract: To determine the contribution of the endoplasmic reticulum (ER) to cell fate decision, we focused on BRI3-binding protein (BRI3BP) residing in this organelle. BRI3BP, when overexpressed, augmented the apoptosis of human embryonic kidney 293T cells challenged with drugs including the anti-cancer agent etoposide. In contrast, the knockdown of BRI3BP reduced the drug-triggered apoptosis. BRI3BP overexpression enhanced both mitochondrial cytochrome c release and caspase-3 activity in etoposide-treated cells. In response to etoposide, the ER reorganized into irregularly shaped lamellae in mock-transfected cells, whereas in BRI3BP-overexpressing cells, such reorganization was not observed. These observations suggest that BRI3BP is involved in the structural dynamics of the ER and affects mitochondrial viability. Taken together, BRI3BP, widely expressed in animal cell types, seems to possess a pro-apoptotic property and can potentiate drug-induced apoptosis.
authors.affiliation: The 21st Century Center of Excellence Program, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. yamazakt@pharm.kyoto-u.ac.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Nozomi
authors.initials: N
authors.lastname: Sasaki
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Daiju
authors.initials: D
authors.lastname: Yamazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikeda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Shinji
authors.initials: S
authors.lastname: Komazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D005047:Etoposide / Q000008:administration & dosage*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D009363:Neoplasm Proteins
chemical_list: D000970:Antineoplastic Agents; C425529:BRI3BP protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D005047:Etoposide