| First Author | Lawson SK | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 1 | Pages | 127-35 |
| PubMed ID | 23109423 | Mgi Jnum | J:192846 |
| Mgi Id | MGI:5466646 | Doi | 10.1128/MCB.00695-12 |
| Citation | Lawson SK, et al. (2013) p38alpha mitogen-activated protein kinase depletion and repression of signal transduction to translation machinery by miR-124 and -128 in neurons. Mol Cell Biol 33(1):127-35 |
| abstractText | The p38alpha to p38delta mitogen-activated protein kinases (MAPKs) are central regulatory nodes coordinating acute stress and inflammatory responses. Their activation leads to rapid adjustment of protein synthesis, for instance translational induction of proinflammatory cytokines. The only known direct link of p38 to translation machinery is the MAPK signal-integrating kinase Mnk. Only p38alpha and p38beta transcripts are ubiquitously expressed. These mRNAs encode highly conserved proteins that equally phosphorylate recombinant Mnk1 in vitro. We discovered that expression of the p38alpha protein, but not the p38beta isoform, is suppressed in the brain. This is due to p38alpha depletion by two neuron-selective microRNAs (miRNAs), miR-124 and -128. Suppression of p38alpha protein was reversed by miR-124/-128 antisense oligonucleotides in primary explant neuronal cultures. Targeted p38alpha depletion reduced Mnk1 activation, which cannot be compensated by p38beta. Our research shows that p38alpha alone controls acute stress and cytokine signaling from p38 MAPK to translation machinery. This regulatory axis is greatly diminished in neurons, which may insulate brain physiology and function from p38alpha-Mnk1-mediated signaling. |
