ArticleProceedings of the National Academy of Sciences of the United States of America1999
p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 199 citations in OpenAlex.
- ML281 Does Not Function as an STK33 Inhibitor but Modulates Proliferation and Differentiation of Keratinocytes Derived from Hypertrophic Scars.International journal of molecular sciences · 2026Article
- Decreased mitochondrial transcription factor A and mitochondrial DNA copy number promote cyclin-dependent kinase inhibitor 1A expression and reduce tumorigenic properties of colorectal cancer cells.Discover oncology · 2024Article
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- The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.Nature communications · 2023Article
- SOCS1 Deficiency Promotes Hepatocellular Carcinoma via SOCS3-Dependent CDKN1A Induction and NRF2 Activation.Cancers · 2023Article
- Functional cooperation between ASK1 and p21Cell death discovery · 2021Article
- Article
- Epidermal ROCK2 induces AKT1/GSK3β/β-catenin, NFκB and dermal tenascin C; but enhanced differentiation and p53/p21 inhibit papilloma.Carcinogenesis · 2020Article
- Multifaceted p21 in carcinogenesis, stemness of tumor and tumor therapy.World journal of stem cells · 2020Review
- Article
- Defining Epidermal Basal Cell States during Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics.Cell reports · 2020Article
- Recognizable neonatal clinical features of aplasia cutis congenita.Italian journal of pediatrics · 2020Article
- A genome-wide long noncoding RNA CRISPRi screen identifiesGenome research · 2020Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- 17-DMAG regulates p21 expression to induce chondrogenesisDisease models & mechanisms · 2018Article
- P21Journal of neuro-oncology · 2018Article
- Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation.The Journal of experimental medicine · 2017Article
- ROCK2/rasOncogene · 2017Article
- DNA damage during S-phase mediates the proliferation-quiescence decision in the subsequent G1 via p21 expression.Nature communications · 2017Article
- CDK inhibitors for muscle stem cell differentiation and self-renewal.The journal of physical fitness and sports medicine · 2017Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
p21(WAF1/Cip1) is one of the best characterized downstream targets of p53, and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established. However, whether p21 exerts a tumor-suppressing function of its own remains to be established. We report here that, similarly to loss of p53, disruption of the p21(WAF1/Cip1) gene results in a markedly increased susceptibility to chemically induced skin carcinoma formation, whereas the number of papillomas is reduced. Previous evidence indicates that malignant versus benign keratinocyte tumor formation is likely to involve distinct target-cell populations with a different commitment to differentiation. In parallel with the increased susceptibility to carcinoma formation, loss of p21(WAF1/Cip1) was found to promote keratinocyte subpopulations with increased growth/differentiation potential, including clonal growth capability, reversible commitment to differentiation, and capability to generate all types of terminally differentiated keratinocytes present in vivo, not only in the interfollicular epidermis but also in hair follicles. Thus, these findings have revealed a function of p21 as a suppressor of malignant but not benign skin-tumor formation and a determinant of the growth/differentiation potential of keratinocyte subpopulations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.