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.
Digital Object Identifier (DOI)
Published in Biochemistry and Cell Biology, Volume 90, Issue 6, 2012.
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