Related Experiment Video
Updated: Nov 15, 2025
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
3.3K
Fine-tuning p53 activity by modulating the interaction between eukaryotic translation initiation factor eIF4E and
Wenqiang Sun1, Kyra Laubach1, Christopher Lucchessi1
1Comparative Oncology Laboratory, School of Veterinary Medicine, School of Medicine, University of California at Davis, Davis, California 95616, USA.
Genes & Development
|March 5, 2021
Summary
The RNA-binding protein RBM38 regulates p53 expression by interacting with eIF4E. Modifying this interaction in cells and mice impacts p53 activity, offering therapeutic potential for cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Protein-RNA Interactions
Background:
- p53 is a crucial tumor suppressor, but its overexpression can be detrimental.
- RNA-binding protein RBM38 is a key regulator of p53 expression.
- RBM38's interaction with eIF4E influences p53 mRNA translation.
Purpose of the Study:
- To investigate the role of the RBM38-eIF4E interaction in controlling p53 activity.
- To generate and analyze RBM38/eIF4E knock-in (KI) cell lines and an Rbm38 S193D KI mouse model.
Main Methods:
- Generation of RBM38/eIF4E knock-in cell lines with specific mutations.
- Creation of an Rbm38 S193D knock-in mouse model.
- Analysis of RBM38-eIF4E binding, p53 expression, and p53-dependent cellular processes.
Main Results:
- Specific RBM38 mutations (S195D, Y192C) enhanced RBM38-eIF4E binding and p53 expression.
- A specific eIF4E mutation (D202K) weakened eIF4E-RBM38 interaction, enhancing p53 expression.
- The Rbm38 S193D KI mouse model exhibited enhanced p53-dependent senescence, shortened lifespan, and increased tumor susceptibility.
Conclusions:
- The RBM38-eIF4E interaction is critical for modulating p53 expression.
- In vivo evidence supports the RBM38-eIF4E loop as a target for fine-tuning p53.
- This regulatory loop holds potential for therapeutic development in cancer and other diseases.
Related Concept Videos
01:23Regulation of Expression at Multiple Steps
1.2K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.2K
01:23Negative Regulator Molecules
37.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.4K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.7K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.7K
02:04Covalently Linked Protein Regulators
8.2K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.2K
02:24Regulation of Expression Occurs at Multiple Steps
24.3K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
24.3K
02:23Abnormal Proliferation
4.9K
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...
4.9K