| First Author | Kim MJ | Year | 2003 |
| Journal | Nat Genet | Volume | 34 |
| Issue | 3 | Pages | 330-6 |
| PubMed ID | 12819782 | Mgi Jnum | J:84078 |
| Mgi Id | MGI:2665161 | Doi | 10.1038/ng1182 |
| Citation | Kim MJ, et al. (2003) Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation. Nat Genet 34(3):330-6 |
| abstractText | p38 is associated with a macromolecular tRNA synthetase complex. It has an essential role as a scaffold for the complex, and genetic disruption of p38 in mice causes neonatal lethality. Here we investigated the molecular mechanisms underlying lethality of p38-mutant mice. p38-deficient mice showed defects in lung differentiation and respiratory distress syndrome. p38 was found to interact with FUSE-binding protein (FBP), a transcriptional activator of c-myc. Binding of p38 stimulated ubiquitination and degradation of FBP, leading to downregulation of c-myc, which is required for differentiation of functional alveolar type II cells. Transforming growth factor-beta (TGF-beta) induced p38 expression and promoted its translocation to nuclei for the regulation of FBP and c-myc. Thus, this work identified a new activity of p38 as a mediator of TGF-beta signaling and its functional importance in the control of c-myc during lung differentiation. |
