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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.

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Yang, X., He, X., Yang, Z., & Jabbari, E. (2012). Mammalian PER2 regulates AKT activation and DNA damage response. Biochemistry And Cell Biology, 90(6), 675-682. doi: 10.1139/o2012-025