AIMP1/p43 downregulates TGF-beta signaling via stabilization of smurf2

作者：Lee Yeon Sook; Han Jung Min; Son Sung Hwa; Choi Jin Woo; Jeon Eun Ju; Bae Suk Chul; Park Young In; Kim Sunghoon^*

来源：Biochemical and Biophysical Research Communications, 2008, 371(3): 395-400.

DOI：10.1016/j.bbrc.2008.04.099

• AIMP1/p43
• aminoacyl-tRNA synthetase
• TGF-beta
• 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.

• 出版日期2008-7-4
• 单位河北医科大学