| First Author | Amatya PN | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1823 |
| Issue | 12 | Pages | 2099-108 |
| PubMed ID | 22982065 | Mgi Jnum | J:192904 |
| Mgi Id | MGI:5466796 | Doi | 10.1016/j.bbamcr.2012.08.022 |
| Citation | Amatya PN, et al. (2012) A role of DNA-dependent protein kinase for the activation of AMP-activated protein kinase in response to glucose deprivation. Biochim Biophys Acta 1823(12):2099-108 |
| abstractText | The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) plays an essential role in double-strand break repair by initially recognizing and binding to DNA breaks. Here, we show that DNA-PKcs interacts with the regulatory gamma1 subunit of AMP-activated protein kinase (AMPK), a heterotrimeric enzyme that has been proposed to function as a "fuel gauge" to monitor changes in the energy status of cells and is controlled by the upstream kinases LKB1 and Ca(2)(+)/calmodulin-dependent kinase kinase (CaMKK). In co-immunoprecipitation analyses, DNA-PKcs and AMPKgamma1 interacted physically in DNA-PKcs-proficient M059K cells but not in DNA-PKcs-deficient M059J cells. Glucose deprivation-stimulated phosphorylation of AMPKalpha on Thr172 and of acetyl-CoA carboxylase (ACC), a downstream target of AMPK, is substantially reduced in M059J cells compared with M059K cells. The inhibition or down-regulation of DNA-PKcs by the DNA-PKcs inhibitors, wortmannin and Nu7441, or by DNA-PKcs siRNA caused a marked reduction in AMPK phosphorylation, AMPK activity, and ACC phosphorylation in response to glucose depletion in M059K, WI38, and IMR90 cells. In addition, DNA-DNA-PKcs(-/-) mouse embryonic fibroblasts (MEFs) exhibited decreased AMPK activation in response to glucose-free conditions. Furthermore, the knockdown of DNA-PKcs led to the suppression of AMPK (Thr172) phosphorylation in LKB1-deficient HeLa cells under glucose deprivation. Taken together, these findings support the positive regulation of AMPK activation by DNA-PKcs under glucose-deprived conditions in mammalian cells. |
