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. 2015 Oct 16;6:8651. doi: 10.1038/ncomms9651

Figure 9. Working model of how SETDB1 regulates cancer cell growth through methylation of p53.

Figure 9

GOF TP53 mutations, such as R249S, are relatively stable and often oncogenic. The stability of these GOF p53 can be enhanced through interaction with and being di-methylated by SETDB1 at K370, which results in less MDM2 association. In cancer cells bearing GOF p53 mutation and SETDB1 overexpression, attenuation of SETDB1 leads to less p53K370me2, enhanced p53 turnover and growth inhibition. Although SETDB1 can also interact with and methylate wild-type p53 at K370, it has little effect on cell growth as the wild type p53 is inherently very unstable and acts as a tumour suppressor. Therefore, SETDB1 can regulate cancer cell growth, at least in part, through methylation of GOF p53 at K370.