The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA damage response in vivo |
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Authors: | Campaner Stefano Spreafico Fabio Burgold Thomas Doni Mirko Rosato Umberto Amati Bruno Testa Giuseppe |
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Affiliation: | Department of Experimental Oncology, European Institute of Oncology at the IFOM-IEO-Campus, Via Adamello 16, 20139 Milan, Italy. |
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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. |
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