Related Experiment Video
Updated: Dec 28, 2025
09:11
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
6.9K
The acetyltransferase p300 regulates NRF2 stability and localization
Athina Ganner1, Zazie-Charlotte Pfeiffer1, Laura Wingendorf1
1Renal Division, Department of Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
Biochemical and Biophysical Research Communications
|February 15, 2020
Summary
The acetyltransferase p300 enhances cellular defense by stabilizing the NRF2 protein, promoting its nuclear entry and protecting cells from oxidative stress. This reveals a new regulatory checkpoint in stress adaptation.
Area of Science:
- Cellular biology
- Molecular mechanisms of stress response
Background:
- The transcription factor NRF2 is crucial for cellular protection against environmental stress and maintaining homeostasis.
- The acetyltransferase p300 is known to enhance NRF2 transcriptional activity as part of the NRF2 complex.
Purpose of the Study:
- To elucidate a novel mechanism by which p300 facilitates NRF2 activity.
- To investigate the interaction between p300 and the NRF2-KEAP1 signaling pathway.
Main Methods:
- Investigated physical interaction between p300 and NRF2.
- Assessed the effect of p300 on NRF2-KEAP1 complex formation.
- Measured NRF2 protein abundance, stability, and nuclear localization.
- Evaluated cell viability under oxidative stress conditions following p300 overexpression.
Main Results:
- p300 directly interacts with NRF2, disrupting the NRF2-KEAP1 complex.
- p300 significantly increases NRF2 protein abundance and stability.
- The acetyltransferase activity of p300 is essential for NRF2 stabilization.
- Overexpression of p300 enhances HEK293T cell resistance to oxidative stress and improves cell viability.
Conclusions:
- p300 regulates NRF2 stability and nuclear localization, thereby modulating NRF2-KEAP1 signaling.
- This interaction represents a novel checkpoint in the cellular adaptation to oxidative stress.
- p300's role in NRF2 regulation offers potential therapeutic targets for stress-related conditions.
More Related Videos
Related Concept Videos
02:04Covalently Linked Protein Regulators
8.5K
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....
8.5K
01:45Regulation of Nuclear Protein Sorting
3.1K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.1K
02:23Master Transcription Regulators
7.6K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K
01:37The Unfolded Protein Response
6.1K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.1K
02:04Co-activators and Co-repressors
8.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.3K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K