Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Mar 1;9(5):947-52.
doi: 10.4161/cc.9.5.10872. Epub 2010 Mar 7.

p53-mediated induction of Noxa and p53AIP1 requires NFkappaB

Jim O'Prey  1 , Diane Crighton, Angel G Martin, Karen H Vousden, Howard O Fearnhead, Kevin M Ryan
Affiliations

p53-mediated induction of Noxa and p53AIP1 requires NFkappaB

Jim O'Prey et al. Cell Cycle. .

Abstract

The intricate regulation of cell survival and cell death is critical for the existence of both normal and transformed cells. Two factors central to these processes are p53 and NFkappaB, with both factors having ascribed roles in both promoting and repressing cell death. Not surprisingly, a number of studies have previously reported interplay between p53 and NFkappaB. The mechanistic basis behind these observations, however, is currently incomplete. We report here further insights into this interplay using a system where blockade of NFkappaB inhibits cell death from p53, but at the same time sensitizes cells to death by TNFalpha. We found in agreement with a recent report showing that NFkappaB is required for the efficient activation of the BH3-only protein Noxa by the p53 family member p73, that p53's ability to induce Noxa is also impeded by inhibition of NFkappaB. In contrast to the regulation by p73, however, blockade of NFkappaB downstream of p53 decreases Noxa protein levels without effects on Noxa mRNA. Our further analysis of the effects of NFkappaB inhibition on p53 target gene expression revealed that while most target genes analysed where unaffected by blockade of NFkappaB, the p53-mediated induction of the pro-apoptotic gene p53AIP1 was significantly dependent on NFkappaB. These studies therefore add further insight into the complex relationship of p53 and NFkappaB. In addition, since both Noxa and p53AIP1 have been shown to be important components of p53-mediated cell death responses, these findings may also indicate critical points where NFkappaB plays a pro-apoptotic role downstream of p53.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources