Control of apoptosis by p53
Abstract
The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert to ensure that the cell death program proceeds efficiently. Moreover, the apoptotic activity of p53 is tightly controlled, and is influenced by a series of quantitative and qualitative events that influence the outcome of p53 activation. Interestingly, other p53 family members can also promote apoptosis, either in parallel or in concert with p53. Although incomplete, our current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type. Understanding this network in more detail will provide insights into cancer and other diseases, and will identify strategies to improve their therapeutic treatment.
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Senescent cells are better able to withstand stresses such as serum deprivation than nonsenescent cells.
“Indeed, senescent cells are better able to withstand stresses such as serum deprivation than nonsenescent cells (Wang, 1995; Fridman & Lowe, 2003).”
From The Achilles' heel of senescent cells: from transcriptome to senolytic drugs (2015) · cites this paper as Fridman & Lowe, 2003
p53 is a transcription factor that responds to several forms of cellular stress.
“p53 is a transcription factor that responds to several forms of cellular stress [5].”
From Preclinical Efficacy of the MDM2 Inhibitor RG7112 in <i>MDM2</i> -Amplified and <i>TP53</i> Wild-type Glioblastomas (2016) · cites this paper as [5]
Beyond a certain level of DNA damage, p53 switches to a pro-apoptotic function, transcriptionally activating a distinct set of gene targets.
“Beyond a certain level of DNA damage, however, p53 switches to a pro-apoptotic function, where it transcriptionally activates a distinct set of gene targets (Fridman and Lowe, 2003).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Fridman and Lowe, 2003
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- Authors
- Fridman, J. S., & Lowe, S. W.
- Affiliations
- Incyte (United States) (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Lowe, Scott W
- ORCID
- Lowe, Scott W
- Venue
- Oncogene
- Published
- 2003-12-08
- Volume
- 22
- Issue
- 56
- Pages
- 9030-9040
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2108966286
- Cited by
- 1,401
- References
- 12
- Citations by year
- 2026: 22 · 2025: 31 · 2024: 55 · 2023: 64 · 2022: 96 · 2021: 78 · 2020: 86 · 2019: 75 · 2018: 76 · 2017: 95 · 2016: 78 · 2015: 78 · 2014: 50 · 2013: 69 · 2012: 51
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- p53, apoptosis, tumor suppressor, transcriptional activation, p53 family, chemoresistance, tumor progression, stress signaling, antiproliferative response
- MeSH terms
- Gene Expression Regulation, Humans, Models, Biological, Neoplasms, Oxidation-Reduction, Transcription, Genetic, Signal Transduction, Genes, p53, Apoptosis
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