Related Experiment Video

Updated: Jul 2, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53

Jung Min Han1, Bum-Joon Park, Sang Gyu Park

  • 1Center for Medicinal Protein Network and Systems Biology, College of Pharmacy, and College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

Proceedings of the National Academy of Sciences of the United States of America
|August 13, 2008
PubMed

Insights

A newly discovered role for AIMP2 (aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2) is its function as a positive regulator of p53. This protein promotes apoptosis in response to DNA damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • AIMP2 (aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2) is known as a scaffolding protein essential for the tRNA synthetase complex.
  • The role of AIMP2 in cellular stress responses, particularly concerning DNA damage, remains largely unexplored.

Purpose of the Study:

  • To elucidate the novel function of AIMP2 in regulating p53 stability and activity under genotoxic stress.
  • To investigate the mechanism by which AIMP2 influences apoptosis induction following DNA damage.

Main Methods:

  • Depletion and reintroduction of AIMP2 in cellular models.
  • Analysis of AIMP2 phosphorylation, subcellular localization, and interaction with p53 and MDM2.
  • Assessment of apoptosis induction and p53 levels following genotoxic stress (e.g., UV radiation).
  • Utilizing Nutlin-3 to modulate p53 activity in AIMP2-deficient cells.

Main Results:

  • AIMP2 depletion confers resistance to DNA damage-induced apoptosis, while its reintroduction restores sensitivity.
  • Upon DNA damage, AIMP2 undergoes phosphorylation, dissociates from the tRNA synthetase complex, and translocates to the nucleus.
  • AIMP2 directly binds to p53, inhibiting MDM2-mediated p53 ubiquitination and degradation.
  • Mutations in AIMP2 that disrupt p53 interaction impair its p53-activating function.
  • Nutlin-3 treatment rescues p53 levels and UV-induced cell death in AIMP2-deficient cells.

Conclusions:

  • AIMP2 acts as a crucial positive regulator of p53 in response to genotoxic stress.
  • AIMP2 functions as a proapoptotic factor by stabilizing p53, thereby linking the translational machinery to DNA damage response pathways.
  • This study reveals a previously unrecognized role for AIMP2 in cancer biology and DNA damage signaling.

More Related Videos

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay13:10

Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay

Published on: June 9, 2017

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...