Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation

Min Jung Kim, Bum Joon Park, Young Sun Kang, Hyoung June Kim, Jae Hyun Park, Jung Woo Kang, Sang Won Lee, Jung Min Han, Han Woong Lee, Sunghoon Kim

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

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-β (TGF-β) 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-β signaling and its functional importance in the control of c-myc during lung differentiation.

Original languageEnglish
Pages (from-to)330-336
Number of pages7
JournalNature Genetics
Volume34
Issue number3
DOIs
Publication statusPublished - 2003 Jul 1

All Science Journal Classification (ASJC) codes

  • Genetics

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