ArticleOncogene2011
Mutant p53 subverts p63 control over KLF4 expression in keratinocytes.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials.Cell death discovery · 2026Review
- Glucocorticoid receptor controls atopic dermatitis inflammation via functional interactions with P63 and autocrine signaling in epidermal keratinocytes.Cell death & disease · 2024Article
- Impact of p53 knockdown on protein dataset of HaCaT cells.Data in brief · 2022Article
- Molecular profile of pure squamous cell carcinoma of the bladder identifies major roles for OSMR and YAP signalling.The journal of pathology. Clinical research · 2022Article
- ΔNp63α promotes Epstein-Barr virus latency in undifferentiated epithelial cells.PLoS pathogens · 2021Article
- Disruption of TP63-miR-27a* Feedback Loop by Mutant TP53 in Head and Neck Cancer.Journal of the National Cancer Institute · 2020Article
- p63 Is a Promising Marker in the Diagnosis of Unusual Skin Cancer.International journal of molecular sciences · 2019Review
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
- Role of FGFR2b expression and signaling in keratinocyte differentiation: sequential involvement of PKCδ and PKCα.Cell death & disease · 2018Article
- Is Ras a potential target in treatment against cutaneous squamous cell carcinoma?Journal of Cancer · 2018Article
- Keratinocytes Isolated From Individual Cleft Lip/Palate Patients Display Variations in Their Differentiation PotentialFrontiers in physiology · 2018Article
- Differentiation-Dependent LMP1 Expression Is Required for Efficient Lytic Epstein-Barr Virus Reactivation in Epithelial Cells.Journal of virology · 2017Article
- KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification.Scientific reports · 2016Article
- KLF4-Mediated Suppression of CD44 Signaling Negatively Impacts Pancreatic Cancer Stemness and Metastasis.Cancer research · 2016Article
- Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells.PLoS pathogens · 2015Article
- ΔNp63 regulates select routes of reprogramming via multiple mechanisms.Cell death and differentiation · 2013Article
- Protein kinase C δ increases Kruppel-like factor 4 protein, which drives involucrin gene transcription in differentiating keratinocytes.The Journal of biological chemistry · 2013Article
- Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes.Cell death & disease · 2012Article
- Gain-of-function p53 mutants have widespread genomic locations partially overlapping with p63.Oncotarget · 2012Article
- p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53.Cell death and differentiation · 2011Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.
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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.