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. 2008 Apr 25;30(2):203-13.
doi: 10.1016/j.molcel.2008.02.024.

PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival

Lana Bozulic  1 , Banu Surucu, Debby Hynx, Brian A Hemmings
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PKBalpha/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival

Lana Bozulic et al. Mol Cell. .
Free article

"V体育安卓版" Abstract

Protein kinase B (PKB/Akt) is a well-established regulator of several essential cellular processes. Here, we report a route by which activated PKB promotes survival in response to DNA insults in vivo VSports手机版. PKB activation following DNA damage requires 3-phosphoinositide-dependent kinase 1 (PDK1) and DNA-dependent protein kinase (DNA-PK). Active PKB localizes in the nucleus of gamma-irradiated cells adjacent to DNA double-strand breaks, where it colocalizes and interacts with DNA-PK. Levels of active PKB inversely correlate with DNA damage-induced apoptosis. A significant portion of p53- and DNA damage-regulated genes are misregulated in cells lacking PKBalpha. PKBalpha knockout mice show impaired DNA damage-dependent induction of p21 and increased tissue apoptosis after single-dose whole-body irradiation. Our findings place PKB downstream of DNA-PK in the DNA damage response signaling cascade, where it provides a prosurvival signal, in particular by affecting transcriptional p21 regulation. Furthermore, this function is apparently restricted to the PKBalpha isoform. .

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