| First Author | González-Terán B | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10477 | PubMed ID | 26795633 |
| Mgi Jnum | J:236071 | Mgi Id | MGI:5804525 |
| Doi | 10.1038/ncomms10477 | Citation | Gonzalez-Teran B, et al. (2016) p38gamma and delta promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation. Nat Commun 7:10477 |
| abstractText | Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown. Here we show that cardiac activation of p38gamma and p38delta increases during postnatal development and by hypertrophy-inducing stimuli. p38gamma/delta promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of p38gamma/delta(-/-) mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of Deptor, or cardiomyocyte overexpression of active p38gamma and p38delta. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR. Our results demonstrate that p38gamma/delta control heart growth by modulating mTOR pathway through DEPTOR phosphorylation and subsequent degradation. |
