AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2.
AIMP1 (also known as p43) is a factor associated with a macromolecular aminoacyl-tRNA synthetase (ARS) complex but also plays diverse regulatory roles in various physiological processes. Here, we report that AIMP1 negatively regulates TGF-beta signaling via stabilization of Smurf2. TGF-beta-dependent phosphorylation and nuclear localization of R-Smads, induction of target genes, and growth arrest were increased in AIMP1-deficient or -suppressed cells. In AIMP1-deficient or suppressed cells, the Smurf2 level was decreased. Various binding assays demonstrated the direction interaction of the C-terminal region of AIMP1 directly with the Smad7-binding region of Smurf2. The association of Smurf2 with Smad7 and its ubiquitination were inhibited by AIMP1, thereby protecting its autocatalytic degradation stimulated by Smad7. Thus, this work suggests the novel activity of AIMP1 as a component of negative feedback loop of TGF-beta signaling.
Lee
Yeon Sook
YS
Division of Life Sciences, Graduate School of Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Han
Jung Min
JM
Son
Sung Hwa
SH
Choi
Jin Woo
JW
Jeon
Eun Ju
EJ
Bae
Suk-Chul
SC
Park
Young In
YI
Kim
Sunghoon
S
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004795:Enzyme Stability; D025461:Feedback, Physiological; D051379:Mice; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
C514492:Aimp1 protein, mouse; D016207:Cytokines; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; C526200:Smurf2 protein, rat; D044767:Ubiquitin-Protein Ligases