A rapid-response stress switch

Kritikou, Ekat

doi:10.1038/nrm2093

Research Highlight
Published: January 2007

Cancer

A rapid-response stress switch

Ekat Kritikou

Nature Reviews Molecular Cell Biology volume 8, page 5 (2007)Cite this article

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The authors first showed that SMYD2 monomethylates p53 at residue K370 in vitro and in vivo. But what is the significance of this modification for p53 function? SMYD2 negatively regulates the expression of p53-responsive genes (such as p21 and Mdm2 ) in a p53-dependent manner, and it does so by downregulating the transcriptional activity of p53. Increased amounts of SMYD2 resulted in reduced p53 binding to the p21 promoter, and decreased levels of promoter-associated p53 correlated with decreasing amounts of p21 mRNA and protein. This indicated that SMYD2-mediated K370 modification reduces the DNA-binding efficiency of p53.

Huang and co-workers also investigated a possible crosstalk between the previously identified SET9-mediated p53-activating K372 modification and the p53-repressing K370 modification. Intriguingly, K372 methylation inhibits K370 methylation in vitro and in vivo. On the basis of these data, the authors proposed that “there is an equilibrium between promoter-bound and free p53.” SMYD2-mediated K370 methylation results in the dissociation of p53 from DNA, whereas SET9-mediated K372 methylation promotes the association of p53 with promoters by blocking SMYD2-mediated methylation.

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