Cited by 858Cancer-related Molecular PathwaysDNA Repair MechanismsCell death mechanisms and regulation

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p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts.

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Agarwal, M L, Agarwal, A, Taylor, W R, Stark, G R·1995·Proceedings of the National Academy of Sciences

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Abstract

Increased expression of wild-type p53 in response to DNA damage arrests cells late in the G1 stage of the cell cycle by stimulating the synthesis of inhibitors of cyclin-dependent kinases, such as p21/WAF1. To study the effects of p53 without the complication of DNA damage, we used tetracycline to regulate its expression in MDAH041 human fibroblasts that lack endogenous p53. When p53 is expressed at a level comparable to that induced by DNA damage in other cells, most MDAH041 cells arrested in G1, but a significant fraction also arrested in G2/M. Cells released from a mimosine block early in S phase stopped predominantly in G2/M in the presence of p53, confirming that p53 can mediate arrest at this stage, as well as in G1. In these cells, there was appreciable induction of p21/WAF1. MDAH041 cells arrested by tetracycline-regulated p53 for as long as 20 days resumed growth when the p53 level was lowered, in striking contrast to the irreversible arrest mediated by DNA damage. Therefore, irreversible arrest must involve processes other than or in addition to the interaction of p53-induced p21/WAF1 with G1 and G2 cyclin-dependent kinases.

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Authors: Agarwal, M. L., Agarwal, A., Taylor, W. R., & Stark, G. R.
Affiliations: Cleveland Clinic (US)
ORCID: Agarwal, A
Taylor, W R
Stark, G R
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1995-08-29
Volume: 92
Issue: 18
Pages: 8493-8497
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.92.18.8493
PMC: PMC41183
OpenAlex: W2016492849
Semantic Scholar: 0dec4b0f37cb7f12a6b4023ec829754468df3935
Cited by: 858
References: 30
Citations by year: 2026: 2 · 2025: 5 · 2024: 13 · 2023: 22 · 2022: 12 · 2021: 18 · 2020: 24 · 2019: 21 · 2018: 22 · 2017: 40 · 2016: 29 · 2015: 28 · 2014: 33 · 2013: 25 · 2012: 25
FWCI: 17.64
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
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/M checkpoint, G1/S checkpoint, cell cycle arrest, p21, cyclin-dependent kinases, mimosine, DNA damage response
MeSH terms: Cell Cycle, Cell Division, Cell Line, Fibroblasts, Gene Expression Regulation, Humans, Genes, p53, Cyclins, Cyclin-Dependent Kinase Inhibitor p21

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p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts.

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