Send to

Choose Destination
Cancer Res. 2016 Jun 1;76(11):3422-36. doi: 10.1158/0008-5472.CAN-15-3255. Epub 2016 Apr 6.

Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2.

Author information

Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
School of Life Science and Biotechnology, Kyungpook National University, Daegu, Korea.
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Department of Cancer Biology, Scripps Research Institute, Florida Campus, Jupiter, Florida.
College of Pharmacy, Yonsei University, Seoul, South Korea.
CHA Research Institutes & CHA Cancer Institute, CHA University, Seongnam, Korea.
Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center