American Association for Cancer Research
00085472can153255-sup-158856_1_supp_3352383_y2d4d3.pptx (719.53 kB)

Supplementary Figure S10 from Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2

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posted on 2023-03-31, 00:06 authored by Dae Gyu Kim, Jin Young Lee, Ji-Hyun Lee, Ha Yeon Cho, Beom Sik Kang, Song-Yee Jang, Myung Hee Kim, Min Guo, Jung Min Han, Seong-Jin Kim, Sunghoon Kim

Predicted positioning of tRNA synthetases that interact with AIMP2 in MSC.


Global Frontier Project

National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea



AIMP2/p38 is a multifunctional tumor suppressor that normally resides in the cytosol as a scaffold protein of the multi-tRNA synthetase complex (MSC). One of the tumor-suppressive functions of AIMP2 is to facilitate ubiquitin-mediated degradation of FUSE-binding protein (FBP, FUBP1), a transcriptional activator of c-Myc. However, the mechanism by which AIMP2 functions within this pathway and its significance in tumorigenesis are uncertain. Here, we report that Smurf2 is responsible for AIMP2-mediated ubiquitination of FBP, and a mutation in AIMP2 that inhibited its nuclear interaction with Smurf2 enhanced cellular transformation and tumorigenesis in vivo. Treatment of HeLa cells with TGFβ resulted in the phosphorylation of AIMP2 on S156, a residue that is exposed on the embedded GST domain of AIMP2. We further found that phospho-AIMP2 dissociated from the MSC and translocated to the nucleus, where it bound to Smurf2, enhancing ubiquitination of FBP. AIMP2 also inhibited nuclear export of Smurf2 to sustain TGFβ signaling. Collectively, these findings present a novel tumor-suppressive interaction between AIMP2 and Smurf2 and suggest that the disruption of this interaction can lead to oncogenic transformation. Cancer Res; 76(11); 3422–36. ©2016 AACR.