The DOI matches its Crossref record; 234 of the 236 references it cites were found in a registry or an index.
p21 in cancer: intricate networks and multiple activities
Open accessAbstract
One of the main engines that drives cellular transformation is the loss of proper control of the mammalian cell cycle. The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. It is well positioned to function as both a sensor and an effector of multiple anti-proliferative signals. This Review focuses on recent advances in our understanding of the regulation of p21 and its biological functions with emphasis on its p53-independent tumour suppressor activities and paradoxical tumour-promoting activities, and their implications in cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“p21 is a potent cell-cycle inhibitor (39)”
From Txnip Enhances Fitness of Dnmt3a -Mutant Hematopoietic Stem Cells via p21 (2022) · cites this paper as [39]
In the citing paper
“CDKN1A (p21, WAF1, CIP1) was among the first p53 target genes11, 12 to be identified and is now recognized as an encoder for a major cell cycle checkpoint control protein.145”
From Census and evaluation of p53 target genes (2017) · cites this paper as [145]
In the citing paper
“As p21 is rarely genetically affected in cancers [1,124]”
From CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication (2020) · cites this paper as [1]
In the citing paper
“Members of the Krüppel-like factor (KLF) transcription factor (TF) family can activate the CDKN1A gene by cooperating with p300-CREBBP (Aliouat-Denis et al., 2005; Abbas and Dutta, 2009).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Abbas and Dutta, 2009
In the citing paper
“p21WAF1/CIP1 can also be activated by p53 independent mechanisms by other stimulators such as nuclear receptors including androgen, vitamin D and retinoid receptors.”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Abbas and Dutta, 2009
In the citing paper
“Although this is the first detectable event, it is more likely that main role of p21 lies in its capacity to trigger pRb-mediated repression of cell cycle regulators (Fig. 2, for more information on p21 functions (see ref. 98 ).”
From Senescence from G2 arrest, revisited (2015) · cites this paper as [98]
In the citing paper
“For example, cyclin-dependent kinase inhibitor 1A (CDKN1A), a tumor suppressor that is downregulated in multiple cancers (106), is targeted by at least 28 miRNAs and many of which are upregulated together in cancers where CDKN1A has been implicated (107).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [106]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Cell cycle, CDKs and cancer: a changing paradigm
Malumbres, M., & Barbacid, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2602 · Cited by 3,957 · cited 1×
“CDK1, at least in some tissues, may be the crucial target of p21 in tumorigenesi”
BackgroundRequirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
Mice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113
Tumor spectrum analysis in p53-mutant mice
Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00002-6 · Cited by 2,051
Xu, X., Yuan, G., Li, Q., Shan, S.-L., & Jiang, S. (2012) · Hepatogastroenterology · doi:10.5754/hge12404 · Cited by 1,825
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820 · cited 1×
“Recent work suggests that tumour regression can be achieved through the reactivation of senescence, for example by restoring p53 functio”
BackgroundPCNA, the Maestro of the Replication Fork
Moldovan, G.-L., Pfander, B., & Jentsch, S. (2007) · Cell · doi:10.1016/j.cell.2007.05.003 · Cited by 1,796
Cellular senescence in cancer and aging.
Collado, M., Blasco, M. A., & Serrano, M. (2007) · Cell · doi:10.1016/j.cell.2007.07.003 · Cited by 1,708
Flagged first, then by citations
2 of the 236 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Martin-Caballero, J., Flores, J. M., Garcia-Palencia, P. & Serrano, M. Tumor susceptibility of p21Waf1/Cip1-deficient mice. Cancer Res. 61, 6234–6238 (2001). This study demonstrates that deletion of Cdkn1a in mice results in spontaneous tumours but with late onset.
Cited by
Sorted by citations
Items 1,001–1,005 of 1,005
Txnip Enhances Fitness of Dnmt3a -Mutant Hematopoietic Stem Cells via p21
Zhang, C. R., Ostrander, E. L., Kukhar, O., Mallaney, C., Sun, J., Haussler, E., Celik, H., Koh, W. K., King, K. Y., Gontarz, P., et al. (2022) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0132 · Cited by 23
Tavarez-Santamaría, Z., Jacobo-Herrera, N. J., Rocha-Zavaleta, L., Zentella-Dehesa, A., Couder-García, B. D. C., & Martínez-Vázquez, M. (2020) · Molecules · doi:10.3390/molecules25081780 · Cited by 22
Dungan, C. M., Wells, J. M., & Murach, K. A. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00553.2022 · Cited by 21
Targeted protein modification as a paradigm shift in drug discovery
Amirian, R., Azadi Badrbani, M., Izadi, Z., Samadian, H., Bahrami, G., Sarvari, S., Abdolmaleki, S., Nabavi, S. M., Derakhshankhah, H., & Jaymand, M. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115765 · Cited by 18
Overview of molecular signatures of senescence and associated resources: pros and cons
Ntintas, O. A., Vagena, S., Pantelis, P., Theocharous, G., Petty, R., Evangelou, K., & Gorgoulis, V. G. (2026) · FEBS Open Bio · doi:10.1002/2211-5463.70134 · Cited by 6
Metadata
- Authors
- Abbas, T., & Dutta, A.
- Affiliations
- University of Virginia (US)
- Corresponding author
- Abbas, Tarek
- Dutta, Anindya
- Venue
- Nature Reviews Cancer
- Published
- 2009-05-14
- Volume
- 9
- Issue
- 6
- Pages
- 400-414
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC2722839
- OpenAlex
- W2162262059
- Cited by
- 2,712
- References
- 236
- Citations by year
- 2026: 99 · 2025: 156 · 2024: 161 · 2023: 206 · 2022: 182 · 2021: 205 · 2020: 204 · 2019: 180 · 2018: 191 · 2017: 196 · 2016: 148 · 2015: 160 · 2014: 142 · 2013: 151 · 2012: 122
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA089406, R01 CA 89406, T32CA009109)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- p21, cyclin-dependent kinase inhibitors, cell cycle arrest, therapeutic target, cell transformation
- MeSH terms
- Animals, Cell Cycle, Humans, Neoplasms, Tumor Suppressor Protein p53, Cyclin-Dependent Kinase Inhibitor p21
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
