ArticleNucleic acids research2010
Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Single-cell atlas of the developing Down syndrome brain cortex.Nature medicine · 2026Article
- The transcription factor PREP1(PKNOX1) regulates nuclear stiffness, the expression of LINC complex proteins and mechanotransduction.Communications biology · 2022Article
- Down syndrome is an oxidative phosphorylation disorder.Redox biology · 2021Article
- Muscle stem cell dysfunction impairs muscle regeneration in a mouse model of Down syndrome.Scientific reports · 2018Article
- P53 Dysfunction in Neurodegenerative Diseases - The Cause or Effect of Pathological Changes?Aging and disease · 2017Review
- What people with Down Syndrome can teach us about cardiopulmonary disease.European respiratory review : an official journal of the European Respiratory Society · 2017Review
- Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility.Cellular and molecular life sciences : CMLS · 2016Review
- Article
- Transcription factor PREP1 induces EMT and metastasis by controlling the TGF-β-SMAD3 pathway in non-small cell lung adenocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Cognitive and pharmacological insights from the Ts65Dn mouse model of Down syndrome.Current opinion in neurobiology · 2012Article
- Tumorigenesis in Down's syndrome: big lessons from a small chromosome.Nature reviews. Cancer · 2012Article
- MiR-1246: a new link of the p53 family with cancer and Down syndrome.Cell cycle (Georgetown, Tex.) · 2012Article
- MEIS1, PREP1, and PBX4 are differentially expressed in acute lymphoblastic leukemia: association of MEIS1 expression with higher proliferation and chemotherapy resistance.Journal of experimental & clinical cancer research : CR · 2011Article
- Characterization of the regulatory region of the zebrafish Prep1.1 gene: analogies to the promoter of the human PREP1.PloS one · 2010Article
- Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21.Journal of biomedical research · 2010Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
PREP1 (PKNOX1) maps in the Down syndrome (DS) critical region of chromosome 21, is overexpressed in some DS tissues and might be involved in the DS phenotype. By using fibroblasts from DS patients and by overexpressing Prep1 in F9 teratocarcinoma and Prep1(i/i) MEF to single out the role of the protein, we report that excess Prep1 increases the sensitivity of cells to genotoxic stress and the extent of the apoptosis directly correlates with the level of Prep1. The apoptotic response of Prep1-overexpressing cells is mediated by the pro-apoptotic p53 protein that we show is a direct target of Prep1, as its depletion reverts the apoptotic phenotype. The induction of p53 overcomes the anti-apoptotic role of Bcl-X(L), previously shown to be also a Prep1 target, the levels of which are increased in Prep1-overexpressing cells as well. Our results provide a rationale for the involvement of PREP1 in the apoptotic phenotype of DS tissues and indicate that differences in Prep1 level can have drastic effects.
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