Augmentation of drug-induced cell death by ER protein BRI3BP.
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.
Yamazaki
Tetsuo
T
The 21st Century Center of Excellence Program, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. yamazakt@pharm.kyoto-u.ac.jp
Sasaki
Nozomi
N
Nishi
Miyuki
M
Yamazaki
Daiju
D
Ikeda
Atsushi
A
Okuno
Yasushi
Y
Komazaki
Shinji
S
Takeshima
Hiroshi
H
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
D000970:Antineoplastic Agents; C425529:BRI3BP protein, human; D002352:Carrier Proteins; D009363:Neoplasm Proteins; D005047:Etoposide