p53 Regulation of G 2 Checkpoint Is Retinoblastoma Protein Dependent
Open accessAbstract
In the present study, we investigated the role of p53 in G(2) checkpoint function by determining the mechanism by which p53 prevents premature exit from G(2) arrest after genotoxic stress. Using three cell model systems, each isogenic, we showed that either ectopic or endogenous p53 sustained a G(2) arrest activated by ionizing radiation or adriamycin. The mechanism was p21 and retinoblastoma protein (pRB) dependent and involved an initial inhibition of cyclin B1-Cdc2 activity and a secondary decrease in cyclin B1 and Cdc2 levels. Abrogation of p21 or pRB function in cells containing wild-type p53 blocked the down-regulation of cyclin B1 and Cdc2 expression and led to an accelerated exit from G(2) after genotoxic stress. Thus, similar to what occurs in p21 and p53 deficiency, pRB loss can uncouple S phase and mitosis after genotoxic stress in tumor cells. These results indicate that similar molecular mechanisms are required for p53 regulation of G(1) and G(2) checkpoints.
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RB is important for p53-dependent downregulation of multiple genes.
“RB, too, is important for p53-dependent downregulation of multiple genes.100, 101, 102, 103”
From Census and evaluation of p53 target genes (2017) · cites this paper as [100]
RB is required for cell cycle arrest.
“As for p21, RB is also required for cell cycle arrest.100, 152”
From Census and evaluation of p53 target genes (2017) · cites this paper as [100]
After DNA damage, G2/M-specific gene expression is reduced in a p53- or pRb-dependent manner.
“Moreover, in response to DNA damage, the expression of G2/M-specific genes is reduced in a p53-or pRb-dependent manner.61,60,62”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [60]
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References 64 · Cited by 161
- Authors
- Flatt, P. M., Tang, L. J., Scatena, C. D., Szak, S. T., & Pietenpol, J. A.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Pietenpol, Jennifer A.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-06-01
- Volume
- 20
- Issue
- 12
- Pages
- 4210-4223
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85790
- OpenAlex
- W2058377017
- Cited by
- 161
- References
- 64
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA070856, CA68485, CA70856, P30CA068485)
- National Institute of Environmental Health Sciences (ES 07028, P30ES000267, T32ES007028)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, G2 checkpoint, retinoblastoma protein, p21, cyclin B1, cdc2, genotoxic stress, ionizing radiation, doxorubicin, cell cycle arrest, DNA damage response
- MeSH terms
- Gene Expression Regulation, Humans, Tumor Cells, Cultured, Tumor Suppressor Protein p53, Retinoblastoma Protein, G2 Phase
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