Regulation of p53 in embryonic stem cells.
Despite an increasing interest in the role of the p53 tumour suppressor protein in embryonic stem cells, not much is known about its regulation in this cell type. We show that the relatively high amount of p53 protein correlates with a higher amount of p53 RNA in ES cells compared to differentiated cells. Moreover, p53 RNA is more stable in embryonic stem cells and the p53 protein is more often transcribed. This is at least partly due to decreased expression of miRNA-125a and 125b in embryonic stem cells. Despite its cytoplasmic localisation, p53 is degraded in 26S proteasomes in embryonic stem cells. This process is controlled by Mdm2, the deubiquitinating enzyme Hausp and Ubc13. In contrast, the E3 ligase PirH2 appears to be less important for the control of p53 in embryonic stem cells. During differentiation, p53 protein and RNA levels are decreased which corresponds to increased expression of miRNA-125a and miRNA-125b.
Solozobova
Valeriya
V
Karlsruher Institute of Technology, Institute of Toxicology and Genetics, PO-Box 3640, 76021 Karlsruhe, Germany.
Blattner
Christine
C
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D016158:Genes, p53; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; D011500:Protein Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D014212:Tretinoin; D003513:Cycloheximide; D046988:Proteasome Endopeptidase Complex