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- Title
Involvement of Bcl-X<sub>L</sub> deamidation in E1A-mediated cisplatin sensitization of ovarian cancer cells.
- Authors
Chang, C.-Y.; Lin, Y.-M.; Lee, W.-P.; Hsu, H.-H.; Chen, E. I. T.
- Abstract
The adenovirus E1A protein has been shown to be involved in the potentiation of apoptosis induced by chemotherapeutic agents, yet the molecular events of E1A-mediated apoptosis are not very clear. A recent report has suggested that deamidation of the Bcl-XL protein inhibits its antiapoptotic ability and leads to apoptosis induced by alkylating agents in Rb-deficient tumor cells. Since Rb is known to interact with E1A, which interrupts Rb's normal function, we examined Bcl-XL deamidation and cell death induced by cisplatin in E1A transfectants. We found that the E1A transfectants became sensitive to cisplatin-induced apoptosis compared to the parental cells, SKOV3.ip1. Our data show that cisplatin treatment induced the modification of Bcl-XL in the E1A transfectants in dosage and time-dependent manner. Furthermore, phosphatase treatment had no effect on the level of Bcl-XL modification, whereas alkaline lysis buffer appeared to induce the same modification of Bcl-XL. Ectopic expression of the deamidated forms of Bcl- XL in SKOV3.ip1 cells revealed that the modification to the Bcl- XL protein molecules was deamidation. Expression of the E1A mutant (dl1108) which contains deletion at CR2 domain suppressed Bcl-XL deamidation and apoptosis induced by cisplatin. We also found that expression of the nondeamidated Bcl-XL protected E1A transfectants from apoptosis. These findings suggest that Bcl-XL deamidation contributes to E1A-mediated cisplatin sensitization in SKOV3.ip1 cells.Oncogene (2006) 25, 2656–2665. doi:10.1038/sj.onc.1209294; published online 5 December 2005
- Subjects
ADENOVIRUSES; CISPLATIN; OVARIAN cancer; CANCER cells; APOPTOSIS
- Publication
Oncogene, 2006, Vol 25, Issue 18, p2656
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1209294