| First Author | Seong HA | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 25 | Pages | 20797-810 |
| PubMed ID | 22532570 | Mgi Jnum | J:193001 |
| Mgi Id | MGI:5467203 | Doi | 10.1074/jbc.M112.347757 |
| Citation | Seong HA, et al. (2012) Murine protein serine-threonine kinase 38 activates p53 function through Ser15 phosphorylation. J Biol Chem 287(25):20797-810 |
| abstractText | Murine protein serine-threonine kinase 38 (MPK38) is a member of the AMP-activated protein kinase-related serine/threonine kinase family. In this study, we show that MPK38 physically associates with p53 via the carboxyl-terminal domain of MPK38 and the central DNA-binding domain of p53. This interaction is increased by 5-fluorouracil or doxorubicin treatment and is responsible for Ser(15) phosphorylation of p53. Ectopic expression of wild-type Mpk38, but not kinase-dead Mpk38, stimulates p53-mediated transcription in a dose-dependent manner and up-regulates p53 targets, including p53, p21, MDM2, and BAX. Consistently, knockdown of MPK38 shows an opposite trend, inhibiting p53-mediated transcription. MPK38 functionally enhances p53-mediated apoptosis and cell cycle arrest in a kinase-dependent manner by stimulating p53 nuclear translocation. We also demonstrate that MPK38-mediated p53 activation is induced by removing MDM2, a negative regulator of p53, from the p53-MDM2 complex as well as by stabilization of interaction between p53 and its positive regulators, including NM23-H1, serine/threonine kinase receptor-associated protein, and 14-3-3. This leads to the enhancement of p53 stability. Together, these results suggest that MPK38 may act as a novel regulator for promoting p53 activity through direct phosphorylation of p53 at Ser(15). |
