ArticlePloS one2014
Cytoplasmic localization of p21 protects trophoblast giant cells from DNA damage induced apoptosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Cytoplasmic p21 promotes stemness of colon cancer cells via activation of the NFκB pathway.Molecular oncology · 2026Article
- Chronic replication stress-mediated genomic instability disrupts placenta development in mice.PLoS genetics · 2026Article
- Cancer and Aging Biomarkers: Classification, Early Detection Technologies and Emerging Research Trends.Biosensors · 2025Review
- Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges.Cells · 2025Review
- Resistance training suppresses accumulation of senescent fibro-adipogenic progenitors and senescence-associated secretory phenotype in aging rat skeletal muscle.GeroScience · 2025Article
- The antagonistic relationship between apoptosis and polyploidy in development and cancer.Seminars in cell & developmental biology · 2024Review
- Functional consequences of somatic polyploidy in development.Development (Cambridge, England) · 2024Review
- The Role of Annexin A1 in DNA Damage Response in Placental Cells: Impact on Gestational Diabetes Mellitus.International journal of molecular sciences · 2023Article
- Cyclin E overexpression in theFrontiers in cell and developmental biology · 2022Article
- Article
- Progesterone depletion results in Lamin B1 loss and induction of cell death in mouse trophoblast giant cells.PloS one · 2021Article
- Transcriptomic analysis reveals differential gene expression, alternative splicing, and novel exons during mouse trophoblast stem cell differentiation.Stem cell research & therapy · 2020Article
- Squamous differentiation requires G2/mitosis slippage to avoid apoptosis.Cell death and differentiation · 2020Article
- Article
- ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.Diagnostic pathology · 2020Article
- LncRNA LUCAT1 as a novel prognostic biomarker for patients with papillary thyroid cancer.Scientific reports · 2019Article
- Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma.Journal of cell communication and signaling · 2019Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- Polyploidy in tissue homeostasis and regeneration.Development (Cambridge, England) · 2018Review
- Mammalian endoreplication emerges to reveal a potential developmental timer.Cell death and differentiation · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Proliferating trophoblast stem cells (TSCs) can differentiate into nonproliferating but viable trophoblast giant cells (TGCs) that are resistant to DNA damage induced apoptosis. Differentiation is associated with selective up-regulation of the Cip/Kip cyclin-dependent kinase inhibitors p57 and p21; expression of p27 remains constant. Previous studies showed that p57 localizes to the nucleus in TGCs where it is essential for endoreplication. Here we show that p27 also remains localized to the nucleus during TSC differentiation where it complements the role of p57. Unexpectedly, p21 localized to the cytoplasm where it was maintained throughout both the G- and S-phases of endocycles, and where it prevented DNA damage induced apoptosis. This unusual status for a Cip/Kip protein was dependent on site-specific phosphorylation of p21 by the Akt1 kinase that is also up-regulated in TGCs. Although cytoplasmic p21 is widespread among cancer cells, among normal cells it has been observed only in monocytes. The fact that it also occurs in TGCs reveals that p57 and p21 serve nonredundant functions, and suggests that the role of p21 in suppressing apoptosis is restricted to terminally differentiated cells.
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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.