Journal
CELL CYCLE
Volume 4, Issue 7, Pages 927-929Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.4.7.1795
Keywords
PTEN; AKT; CHK1; phosphorylation; ubiquitin; DNA damage
Categories
Funding
- NCI NIH HHS [R01 CA082783-02, R01 CA082783-03, R01 CA082783-04, R01 CA082783, R01 CA082783-01A2] Funding Source: Medline
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CHK1 is an essential kinase involved in the regulation of the cell cycle progression and preservation of genomic integrity. Inhibition of CHK1 leads to the accumulation of double-stranded DNA breaks. Loss of PTEN impairs CHK1-mediated checkpoint activation due to cytoplasmic sequestration of ubiquitinated CHK1. Here, we provide evidence that another consequence of reduced CHK1 function in PTEN deficient cells is the accumulation of double-stranded DNA breaks. Moreover, we show that the site of CHK1 ubiquitination (K274) is near the site of AKT phosphorylation (S280). Overall, these data demonstrate that lack of PTEN generates DNA damage due to inappropriate inactivation of CHK1. DNA damage due to the loss of PTEN is likely to stimulate tumor development.
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