The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Linking the p53 tumour suppressor pathway to somatic cell reprogramming
Open accessAbstract
Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.
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“Knocking down p53 by shRNA increased the efficiency of cell reprogramming.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [79]
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“Recently we, and others, showed that p53 activation contributed to the low frequency of generating induced pluripotent stem cells (iPS) during cell reprogramming [79,80].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [79]
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Metadata
- Authors
- Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M., & Belmonte, J. C. I.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Wahl, Geoffrey M.
- Belmonte, Juan Carlos Izpisúa
- Venue
- Nature
- Published
- 2009-08
- Volume
- 460
- Issue
- 7259
- Pages
- 1140-1144
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2735889
- OpenAlex
- W2070672434
- Cited by
- 1,115
- References
- 40
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 30 · 2023: 34 · 2022: 31 · 2021: 36 · 2020: 29 · 2019: 41 · 2018: 55 · 2017: 60 · 2016: 65 · 2015: 77 · 2014: 96 · 2013: 111 · 2012: 136
- FWCI
- 57.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R33HL088293)
- National Cancer Institute (R01CA100845, R01CA061449)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- p53, somatic cell reprogramming, induced pluripotent stem cells, Oct4, SOX2, p21, Nutlin-3, reprogramming efficiency, malignant transformation, fibroblasts, oncogenes, apoptosis
- MeSH terms
- Animals, Cells, Cultured, Embryo, Mammalian, Female, Fibroblasts, Humans, Male, Mice, Inbred C57BL, Down-Regulation, Keratinocytes, Tumor Suppressor Protein p53, Pluripotent Stem Cells, Cyclin-Dependent Kinase Inhibitor p21, Mice, Cellular Reprogramming
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