Related Experiment Video
Updated: Mar 21, 2026

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2
Dae Gyu Kim1, Jin Young Lee1, Ji-Hyun Lee1
1Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul, Korea.
Abstract:
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.
Insights
A novel tumor suppressor interaction between AIMP2 and Smurf2 was discovered. Disruption of this interaction promotes cellular transformation and tumorigenesis, highlighting a new pathway in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- AIMP2/p38 acts as a tumor suppressor by degrading FUSE-binding protein (FBP), a c-Myc activator.
- The precise mechanism of AIMP2's tumor-suppressive function and its role in tumorigenesis remain unclear.
Purpose of the Study:
- To elucidate the mechanism of AIMP2-mediated FBP degradation.
- To investigate the interaction between AIMP2 and Smurf2 in tumor suppression.
- To determine the significance of this interaction in tumorigenesis.
Main Methods:
- Investigated the role of Smurf2 in AIMP2-mediated ubiquitination of FBP.
- Analyzed the effect of AIMP2 mutations on cellular transformation and in vivo tumorigenesis.
- Examined the impact of TGFβ treatment on AIMP2 phosphorylation and localization.
- Studied the interaction between phosphorylated AIMP2 and Smurf2 in the nucleus.
Main Results:
- Smurf2 mediates AIMP2-induced ubiquitination and degradation of FBP.
- A mutation preventing AIMP2-Smurf2 nuclear interaction increased tumorigenesis.
- TGFβ induced AIMP2 phosphorylation at S156, causing nuclear translocation and Smurf2 binding.
- Phospho-AIMP2 enhanced FBP ubiquitination and inhibited Smurf2 nuclear export, sustaining TGFβ signaling.
Conclusions:
- A novel tumor-suppressive pathway involving AIMP2 and Smurf2 has been identified.
- The AIMP2-Smurf2 interaction is crucial for suppressing FBP-mediated oncogenic transformation.
- Disruption of this interaction contributes to tumorigenesis, offering potential therapeutic targets.
More Related Videos
04:56Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Related Concept Videos
Abnormal Proliferation
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...