The complexity of p53 stabilization and activation
Open accessAbstract
A number of proteins are activated by stress stimuli but none so spectacularly or with the degree of complexity as the tumour suppressor p53 (human p53 gene or protein). Once stabilized, p53 is responsible for the transcriptional activation of a series of proteins involved in cell cycle control, apoptosis and senescence. This protein is present at low levels in resting cells but after exposure to DNA-damaging agents and other stress stimuli it is stabilized and activated by a series of post-translational modifications that free it from MDM2 (mouse double minute 2 but used interchangeably to denote human also), a ubiquination ligase that ubiquitinates it prior to proteasome degradation. The stability of p53 is also influenced by a series of other interacting proteins. In this review, we discuss the post-translational modifications to p53 in response to different stresses and the consequences of these changes.
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p53 activity as an upstream transcription factor of p21 is directly regulated by stress-sensing signalling pathways.
“Additionally, p53 activity as an upstream transcription factor of p21 is directly regulated by stress-sensing signalling pathways [22].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [22]
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- Authors
- Lavin, M. F., & Gueven, N.
- Affiliations
- The University of Queensland (AU)
- QIMR Berghofer Medical Research Institute (AU)
- Corresponding author
- Lavin, M F
- ORCID
- Venue
- Cell Death & Differentiation
- Published
- 2006-04-07
- Volume
- 13
- Issue
- 6
- Pages
- 941-950
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1993170641
- Cited by
- 701
- References
- 102
- Citations by year
- 2026: 13 · 2025: 27 · 2024: 26 · 2023: 23 · 2022: 28 · 2021: 30 · 2020: 27 · 2019: 18 · 2018: 25 · 2017: 22 · 2016: 29 · 2015: 27 · 2014: 39 · 2013: 40 · 2012: 45
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- p53, MDM2, post-translational modification, protein stabilization, ubiquitination, proteasomal degradation, DNA damage response, stress response, transcriptional activation, apoptosis, cell cycle regulation, senescence, tumour suppressor
- MeSH terms
- Acetylation, Animals, Cell Cycle, DNA, DNA Damage, Humans, Mutagens, Phosphorylation, Poly(ADP-ribose) Polymerases, Protein Kinases, Protein Processing, Post-Translational, Tumor Suppressor Protein p53, Apoptosis, Ubiquitin, Proto-Oncogene Proteins c-mdm2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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