Lee Yeon Sook, Han Jung Min, Son Sung Hwa, Choi Jin Woo, Jeon Eun Ju, Bae Suk-Chul, Park Young In, Kim Sunghoon
Division of Life Sciences, Graduate School of Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Biochem Biophys Res Commun. 2008 Jul 4;371(3):395-400. doi: 10.1016/j.bbrc.2008.04.099. Epub 2008 Apr 28.
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.
AIMP1（也称为p43）是一种与大分子氨酰tRNA合成酶（ARS）复合物相关的因子，但在各种生理过程中也发挥着多种调节作用。在此，我们报告AIMP1通过稳定Smurf2负向调节TGF-β信号通路。在AIMP1缺陷或受抑制的细胞中，TGF-β依赖的R-Smads磷酸化和核定位、靶基因诱导以及生长停滞均增加。在AIMP1缺陷或受抑制的细胞中，Smurf2水平降低。各种结合试验表明AIMP1的C末端区域直接与Smurf2的Smad7结合区域相互作用。AIMP1抑制Smurf2与Smad7的结合及其泛素化，从而保护其免受Smad7刺激的自催化降解。因此，这项工作表明AIMP1作为TGF-β信号负反馈环的一个组成部分具有新的活性。
