Mammalian PER2 regulates AKT activation and DNA damage response.
PER2 is a key mammalian circadian clock protein. It also has a tumor suppressive function. Down regulation of PER2 in the cultured cancer cells accelerates cell proliferation, while overexpression of PER2 inhibits cell growth and induces apoptosis. The Per2 mutant mice have a cancer prone phenotype and an altered DNA damage response. Here we report that PER2 regulates AKT activity. Cells with down-regulated PER2 expression have prolonged high levels of AKT T308 phosphorylation after growth factor stimulation or DNA damage. PER2 down-regulation delays DNA damage induced Chk2 activation and overrides DNA damage induced apoptosis and cell cycle arrest.
Dorn Research Institute, 6439 Garners Ferry Rd, Columbia, SC 29209, USA. xiaoming.yang@va.gov
Xiaoming
X
Yang
Xuezhong
X
He
Zhengguan
Z
Yang
Esmaiel
E
Jabbari
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004249:DNA Damage; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008322:Mammals / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
C421902:PER2 protein, human; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D051057:Proto-Oncogene Proteins c-akt