p53-Dependent Transcription and Tumor Suppression Are Not Affected in Set7/9-Deficient Mice

SummaryMethylation 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.

► A Set7/9-deficient mouse strain shows different p53 regulation from that reported by Kurash et al. (2008) ► Mouse p53K369me1 cannot be detected using an antiserum against human p53K372me1 ► Induction of p53 target genes is unaltered in Set7/9−/− primary mouse cells ► p53-dependent apoptosis and cell-cycle arrest are not impaired in Set7/9−/− cells