Nature Genetics34, 330 - 336 (2003)
Published online: 22 June 2003; | doi:10.1038/ng1182
Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation
Min Jung Kim1, Bum-Joon Park1, Young-Sun Kang1, Hyoung June Kim1, Jae-Hyun Park1, Jung Woo Kang1, Sang Won Lee1, Jung Min Han2, Han-Woong Lee3
& Sunghoon Kim1
1
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
2
Imagene, Biotechnology Incubation Center, Seoul National University, Seoul 151-742, Korea.
3
Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Korea.
Correspondence should be addressed to Sunghoon Kim sungkim@snu.ac.kr
p38 is associated with a macromolecular tRNA synthetase complex1. It has an essential role as a scaffold for the complex, and genetic disruption of p38 in mice causes neonatal lethality2. 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-myc3. 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- (TGF-) 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- signaling and its functional importance in the control of c-myc during lung differentiation.
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