title: The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA damage response in vivo.
abstract: p53 is the central regulator of cell fate following genotoxic stress and oncogene activation. Its activity is controlled by several posttranslational modifications. Originally defined as a critical layer of p53 regulation in human cell lines, p53 lysine methylation by Set7/9 (also called Setd7) was proposed to fulfill a similar function in vivo in the mouse, promoting p53 acetylation, stabilization, and activation upon DNA damage (Kurash et al., 2008). We tested the physiological relevance of this circuit in an independent Set7/9 knockout mouse strain. Deletion of Set7/9 had no effect on p53-dependent cell-cycle arrest or apoptosis following sublethal or lethal DNA damage induced by radiation or genotoxic agents. Set7/9 was also dispensable for p53 acetylation following irradiation. c-myc oncogene-induced apoptosis was also independent of Set7/9, and analysis of p53 target genes showed that Set7/9 is not required for the p53-dependent gene expression program. Our data indicate that Set7/9 is dispensable for p53 function in the mouse.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology at the IFOM-IEO-Campus, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Campaner
authors.forename: Fabio
authors.initials: F
authors.lastname: Spreafico
authors.forename: Thomas
authors.initials: T
authors.lastname: Burgold
authors.forename: Mirko
authors.initials: M
authors.lastname: Doni
authors.forename: Umberto
authors.initials: U
authors.lastname: Rosato
authors.forename: Bruno
authors.initials: B
authors.lastname: Amati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Testa
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004249:DNA Damage; D017353:Gene Deletion; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase; D051379:Mice; D018345:Mice, Knockout; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C562044:Setd7 protein, mouse