Related Experiment Video
Updated: Feb 13, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
10.1K
2A-DUB/Mysm1 Regulates Epidermal Development in Part by Suppressing p53-Mediated Programs.
Christina Wilms1, Ioanna Krikki2, Adelheid Hainzl3
1Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, Germany. christinawilms@gmx.net.
International Journal of Molecular Sciences
|March 3, 2018
Summary
The histone H2A deubiquitinase 2A-DUB/Mysm1 is crucial for skin development. Its absence leads to skin atrophy by promoting p53-mediated inhibition, which can be reversed by removing p53.
Area of Science:
- Dermatology and Epigenetics
- Molecular Biology
- Developmental Biology
Background:
- Epidermal development relies on transcription factors and epigenetic modifiers.
- Histone H2A deubiquitinase 2A-DUB/Mysm1 is an epigenetic regulator.
- Its role in skin homeostasis is not well understood.
Purpose of the Study:
- To investigate the function of 2A-DUB/Mysm1 in skin development and homeostasis.
- To analyze the effects of Mysm1 deficiency on epidermal structure and function.
- To identify molecular mechanisms underlying Mysm1's role in the epidermis.
Main Methods:
- Systematic analysis of Mysm1-deficient mice and skin-derived epidermal cells.
- Morphological and histological examination of skin.
- Assessment of cell proliferation, apoptosis, and DNA damage (γH2AX).
- In vitro colony formation assays for epidermal progenitors.
- Molecular analysis to identify interacting proteins and pathways.
- Generation and analysis of Mysm1-/-p53-/- double-deficient mice.
Main Results:
- Mysm1-deficient mice exhibited atrophic skin with reduced thickness and cellularity.
- Decreased epidermal and hair follicle proliferation, increased apoptosis, and elevated γH2AX levels were observed.
- Reduced numbers of epidermal stem cells (α6-Integrinhigh+CD34+) and impaired progenitor colony formation in vitro.
- p53 was identified as a key mediator, driving pro-apoptotic and anti-proliferative gene expression.
- Complementation of Mysm1 deficiency with p53 deficiency rescued skin atrophy.
Conclusions:
- 2A-DUB/Mysm1 plays a critical role in suppressing p53-mediated inhibitory programs during epidermal development.
- Mysm1 is essential for maintaining epidermal homeostasis and proper skin barrier function.
- Targeting Mysm1 or its downstream pathways could offer therapeutic strategies for skin development disorders.
Related Concept Videos
01:23Negative Regulator Molecules
38.6K
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.
38.6K
02:04Covalently Linked Protein Regulators
9.7K
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....
9.7K
02:58Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
01:46Epigenetic Regulation
33.9K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.9K
02:23Master Transcription Regulators
7.8K
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...
7.8K
02:24Regulation of Expression Occurs at Multiple Steps
26.5K
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...
26.5K