Identification of a novel pro-apopotic function of NF-kappaB in the DNA damage response.

ABSTRACT: NF-kappaB is activated by DNA-damaging anticancer drugs as part of the cellular stress response. However, the consequences of drug-induced NF-kappaB activation are still only partly understood. To investigate the impact of NF-kappaB on the cell's response to DNA damage, we engineered glioblastoma cells that stably express mutant IkappaBalpha superrepressor (IkappaBalpha-SR) to block NF-kappaB activation. Here, we identify a novel pro-apoptotic function of NF-kappaB in the DNA damage response in glioblastoma cells. Chemotherapeutic drugs that intercalate into DNA and inhibit topoisomerase II such as Doxorubicin, Daunorubicin and Mitoxantrone stimulate NF-kappaB DNA binding and transcriptional activity prior to induction of cell death. Importantly, specific inhibition of drug-induced NF-kapp

SUBMITTER: Karl S 

PROVIDER: S-EPMC4496130 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature