Biochemical and biophysical research communications, 2013-01, Vol.430 (1), p.208-212
2013
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- Autor(en) / Beteiligte
- Titel
- Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1
- Ist Teil von
- Biochemical and biophysical research communications, 2013-01, Vol.430 (1), p.208-212
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2013
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- ► EGCG down-regulated UHRF1 and DNMT1 expressions in jurkat cells. ► Down-regulation of UHRF1 enhanced expression of p16INK4A and p73. ► UHRF1 over-expression counteracted EGCG-induced apoptosis and G1 arrested cells. ► Mutants of the SRA domain of UHRF1 were unable to down-regulate p16INK4A and p73. Ubiquitin-like containing PHD and Ring finger 1 (UHRF1) contributes to silencing of tumor suppressor genes by recruiting DNA methyltransferase 1 (DNMT1) to their hemi-methylated promoters. Conversely, demethylation of these promoters has been ascribed to the natural anti-cancer drug, epigallocatechin-3-gallate (EGCG). The aim of the present study was to investigate whether the UHRF1/DNMT1 pair is an important target of EGCG action. Here, we show that EGCG down-regulates UHRF1 and DNMT1 expression in Jurkat cells, with subsequent up-regulation of p73 and p16INK4A genes. The down-regulation of UHRF1 is dependent upon the generation of reactive oxygen species by EGCG. Up-regulation of p16INK4A is strongly correlated with decreased promoter binding by UHRF1. UHRF1 over-expression counteracted EGCG-induced G1-arrested cells, apoptosis, and up-regulation of p16INK4A and p73. Mutants of the Set and Ring Associated (SRA) domain of UHRF1 were unable to down-regulate p16INK4A and p73, either in the presence or absence of EGCG. Our results show that down-regulation of UHRF1 is upstream to many cellular events, including G1 cell arrest, up-regulation of tumor suppressor genes and apoptosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-291XeISSN: 1090-2104DOI: 10.1016/j.bbrc.2012.11.087Titel-ID: cdi_hal_primary_oai_HAL_hal_00789025v1
- Format
- –
- Schlagworte
- Apoptosis, Apoptosis - drug effects, Biochemistry, Molecular Biology, Catechin - analogs & derivatives, Catechin - pharmacology, CCAAT-Enhancer-Binding Proteins - antagonists & inhibitors, CCAAT-Enhancer-Binding Proteins - metabolism, Cell Cycle - drug effects, Cellular Biology, Cyclin-Dependent Kinase Inhibitor p16 - genetics, Demethylation, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases - antagonists & inhibitors, DNA (Cytosine-5-)-Methyltransferases - metabolism, DNA methyltransferase, DNA methyltransferase 1, DNA-Binding Proteins - genetics, DNMT1 protein, Down-Regulation, Drugs, Epigallocatechin-3-gallate, Gene Expression Regulation, Neoplastic - drug effects, Genes, Tumor Suppressor - drug effects, Humans, INK4a protein, Jurkat Cells, Life Sciences, Nuclear Proteins - genetics, Overexpression, p16 protein, P16INK4A, Promoter Regions, Genetic, Promoters, Reactive oxygen species, Reactive Oxygen Species - metabolism, Tumor Protein p73, Tumor suppressor gene, Tumor suppressor genes, Tumor Suppressor Proteins - genetics, Ubiquitin-like containing PHD and Ring finger 1, Vascular Endothelial Growth Factor A - metabolism