title: p53-dependent transcription and tumor suppression are not affected in Set7/9-deficient mice.
abstract: Methylation of specific lysine residues in the C terminus of p53 is thought to govern p53-dependent transcription following genotoxic and oncogenic stress. In particular, Set7/9 (KMT7)-mediated monomethylation of human p53 at lysine 372 (p53K372me1) was suggested to be essential for p53 activation in human cell lines. This finding was confirmed in a Set7/9 knockout mouse model (Kurash et al., 2008). In an independent knockout mouse strain deficient in Set7/9, we have investigated its involvement in p53 regulation and find that cells from these mice are normal in their ability to induce p53-dependent transcription following genotoxic and oncogenic insults. Most importantly, we detect no impairment in canonical p53 functions in these mice, indicating that Set7/9-mediated methylation of p53 does not seem to represent a major regulatory event and does not appreciably control p53 activity in vivo.
authors.affiliation: University of British Columbia, Biomedical Research Centre, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lehnertz
authors.forename: Jason C
authors.initials: JC
authors.lastname: Rogalski
authors.forename: Felix M
authors.initials: FM
authors.lastname: Schulze
authors.forename: Lin
authors.initials: L
authors.lastname: Yi
authors.forename: Shujun
authors.initials: S
authors.lastname: Lin
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kast
authors.forename: Fabio M V
authors.initials: FM
authors.lastname: Rossi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle; D016922:Cellular Senescence / Q000235:genetics; D005786:Gene Expression Regulation; D011495:Histone-Lysine N-Methyltransferase; D051379:Mice; D008810:Mice, Inbred C57BL; D011496:Protein Methyltransferases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D016159:Tumor Suppressor Protein p53; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C562044:Setd7 protein, mouse