title: Knockdown of p53 suppresses Nanog expression in embryonic stem cells.
abstract: Mouse embryonic stem cells (ESCs) express high levels of cytoplasmic p53. Exposure of mouse ESCs to DNA damage leads to activation of p53, inducing Nanog suppression. In contrast to earlier studies, we recently reported that chemical inhibition of p53 suppresses ESC proliferation. Here, we confirm that p53 signaling is involved in the maintenance of mouse ESC self-renewal. RNA interference-mediated knockdown of p53 induced downregulation of p21 and defects in ESC proliferation. Furthermore, p53 knockdown resulted in a significant downregulation in Nanog expression at 24 and 48 h post-transfection. p53 knockdown also caused a reduction in Oct4 expression at 48 h post-transfection. Conversely, exposure of ESCs to DNA damage caused a higher reduction of Nanog expression in control siRNA-treated cells than in p53 siRNA-treated cells. These data show that in the absence of DNA damage, p53 is required for the maintenance of mouse ESC self-renewal by regulating Nanog expression.
authors: Qatar Biomedical Research Institute, Qatar Foundation, Doha 5825, Qatar; Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan; Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt. Electronic address: emohamed@qf.org.qa.
authors: Essam Mohamed
authors: EM
authors: Abdelalim
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors: Ikuo
authors: I
authors: Tooyama
mesh_terms: D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055785:Gene Knockdown Techniques / Q000379:methods; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D000071317:Nanog Homeobox Protein; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D016159:Tumor Suppressor Protein p53
keywords: DNA damage; ESCs; Knockdown; Oct4; Self-renewal; Tumor suppressor gene