Cited by 2,113Cancer-related Molecular PathwaysDNA Repair MechanismsCell death mechanisms and regulation

Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control

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Deng, Chuxia, Zhang, Pumin, Wade Harper, J., Elledge, Stephen J., Leder, Philip·1995·Cell

Abstract

p21CIP1/WAF1 is a CDK inhibitor regulated by the tumor suppressor p53 and is hypothesized to mediate G1 arrest. p53 has been suggested to derive anti-oncogenic properties from this relationship. To test these notions, we created mice lacking p21CIP1/WAF1. They develop normally and (unlike p53-/- mice) have not developed spontaneous malignancies during 7 months of observation. Nonetheless, p21-/- embryonic fibroblasts are significantly deficient in their ability to arrest in G1 in response to DNA damage and nucleotide pool perturbation. p21-/- cells also exhibit a significant growth alteration in vitro, achieving a saturation density as high as that observed in p53-/- cells. In contrast, other aspects of p53 function, such as thymocytic apoptosis and the mitotic spindle checkpoint, appear normal. These results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and the anti-oncogenic effects of p53 are more complex.

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Crossref · 10.1016/0092-8674(95)90039-x

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  • p21 is required for p53-mediated G1/S cell cycle arrest.

    “p21 is required for p53-mediated G1/S146, 147, 148 and also for G2/M cell cycle arrest.149”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [148]

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Authors
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P.
Affiliations
  • Baylor College of Medicine (US)
  • Howard Hughes Medical Institute (US)
Venue
Cell
Publisher
Elsevier BV
Published
1995-08
Volume
82
Issue
4
Pages
675-684
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2044057392
Cited by
2,113
References
70
Citations by year
2026: 20 · 2025: 20 · 2024: 32 · 2023: 32 · 2022: 34 · 2021: 40 · 2020: 38 · 2019: 40 · 2018: 43 · 2017: 36 · 2016: 37 · 2015: 34 · 2014: 57 · 2013: 39 · 2012: 65
FWCI
61.04
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute on Aging (AG11085, R01AG011085)
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
p21, p53, G1/S checkpoint, cyclin-dependent kinase inhibitors, DNA damage response, embryonic fibroblasts, cell growth, thymocyte apoptosis, mitotic spindle checkpoint, tumor suppression
MeSH terms
Animals, Base Sequence, Cell Differentiation, Cell Division, Cell Line, DNA, DNA Damage, Spindle Apparatus, Molecular Sequence Data, Neoplasms, Experimental, Genes, p53, Tumor Suppressor Protein p53, G1 Phase, Cyclins, Apoptosis, Cyclin-Dependent Kinase Inhibitor p21, Mice

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