Regulation of the Ku70-Bax complex in Cells.
[摘要] Using a neuronal cell type (N-type) of neuroblastoma (NB) cells, we have proposed a model in which Ku70, a nuclear DNA repair factor, also regulates a pro-apoptotic protein, Bax, by binding to and blocking Bax-dependent cell death activity in the cytosol. Ku70-Bax binding is regulated by Ku70 acetylation such that when Ku70 is acetylated, Bax dissociates from Ku70, triggering cell death. Some studies have suggested that stoichiometry binding of Bax to Ku70 is critical for this regulation. However, this is not consistent with current literature in which Bax is found to be inactive and monomeric in the cytosol. In this project, I have addressed this issue by determining whether all Bax binds to Ku70 in the NB N-type cells. Furthermore, we have also demonstrated that in NB N-type cells, Ku70 depletion triggers Bax-dependent cell death, suggesting that Ku70 may act as a survival factor. I have also addressed the question whether Ku70 acts as a survival factor in other cell types. Our results showed that in the N-type NB cells only a small fraction of Ku70 binds to a small fraction of Bax; the majority of Bax is monomeric. Interestingly, the majority of Ku70 is in several high molecular weight complexes, and there is no free Ku70 in the cytosol in these cells suggesting that the availability of Ku70 may be another factor that regulates Bax activity. Also, my results show that Ku70 may not be required for survival in some cell types because Ku70 depletion does not affect survival. Furthermore, Ku70 acetylation does not dissociate or activate Bax in these Ku70-depletion insensitive cells
[发布日期] [发布机构] University of Michigan
[效力级别] Biological Chemistry [学科分类]
[关键词] Regulation of Ku70-Bax in cells;Biological Chemistry;Science;Biological Chemistry [时效性]