p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1

• DOI: 10.1073/pnas.0406286101
• Publication Date: 2004-09-22T01:16:43Z
• Authors: Han You; YingJu Jang; Annick Itie You-Ten; Hitoshi Okada; Jennifer Liepa; Andrew Wakeham; Kathrin Zaugg; Tak W. Mak
• Keywords: SGK1; Transcription; Crosstalk

FKHRL1 (FOXO3a) and p53 are two potent stress-response regulators. Here we show that these transcription factors exhibit "crosstalk" in vivo. In response to DNA damage, activation led phosphorylation subcellular localization change, which resulted inhibition of activity. AKT was dispensable for p53-dependent suppression FKHRL1. By contrast, serum- glucocorticoid-inducible kinase 1 (SGK1) significantly induced a manner after this induction through extracellular signal-regulated 1/2-mediated posttranslational regulation. Furthermore, SGK1 expression by small interfering RNA knockdown experiment decreased damage. Taken together, our observations reveal previously unrecognized crosstalk between Moreover, findings suggest new pathway understanding aging the age dependency human diseases governed factors.