Akt3 induces oxidative stress and DNA damage by activating the NADPH oxidase via phosphorylation of p47^phox.

ABSTRACT: Akt activation up-regulates the intracellular levels of reactive oxygen species (ROS) by inhibiting ROS scavenging. Of the Akt isoforms, Akt3 has also been shown to up-regulate ROS by promoting mitochondrial biogenesis. Here, we employ a set of isogenic cell lines that express different Akt isoforms, to show that the most robust inducer of ROS is Akt3. As a result, Akt3-expressing cells activate the DNA damage response pathway, express high levels of p53 and its direct transcriptional target miR-34, and exhibit a proliferation defect, which is rescued by the antioxidant N-acetylcysteine. The importance of the DNA damage response in the inhibition of cell proliferation by Akt3 was confirmed by Akt3 overexpression in p53 ^-/- and INK4a ^-/-/Arf

SUBMITTER: Polytarchou C 

PROVIDER: S-EPMC7682348 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature