Please use this identifier to cite or link to this item:
|Title:||p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis|
|Citation:||Kho, P.S., Wang, Z., Zhuang, L., Li, Y., Chew, J.-L., Ng, H.-H., Liu, E.T., Yu, Q. (2004-05-14). p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis. Journal of Biological Chemistry 279 (20) : 21183-21192. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M311912200|
|Abstract:||By using a genome-wide approach, we sought the identification of p53-regulated genes involved in cellular apoptosis. To this end, we assessed the transcriptional response of HCT116 colorectal cancer cells during apoptosis induced by the anticancer drug 5-fluorouracil as the function of p53 status, and we identified 230 potential targets that are regulated by p53. Previously identified p53 targets known to be involved in growth arrest and apoptosis were observed to be induced, thus validating the approach. Strikingly, we found that p53 regulates gene expression primarily through transcriptional repression (n = 189) rather than activation (n = 41), and selective blockade of p53-dependent gene repression resulted in the reduction in 5-fluorouracil-induced apoptosis. Reporter and chromatin immunoprecipitation assays demonstrated that p53 can suppress the promoter activities of three further studied candidate genes PLK, PTTG1, and CHEK1 but would only bind directly to PTTG1 and CHEK1 promoters, revealing that p53 can repress gene expression through both direct and indirect mechanisms. Moreover, RNAi-mediated knockdown of PLK and PTTG1 expression was sufficient to induce apoptosis, suggesting that repression of novel anti-apoptotic genes by p53 might contribute to a significant portion of the p53-dependent apoptosis. Our data support the divergent functions of p53 in regulating gene expression that play both synergistic and pleiotropic roles in p53-associated apoptosis.|
|Source Title:||Journal of Biological Chemistry|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jun 14, 2018
WEB OF SCIENCETM
checked on May 9, 2018
checked on Jun 8, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.