| First Author | Wang Y | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 6 | Pages | 110794 |
| PubMed ID | 35545041 | Mgi Jnum | J:326401 |
| Mgi Id | MGI:7284671 | Doi | 10.1016/j.celrep.2022.110794 |
| Citation | Wang Y, et al. (2022) SETD4-mediated KU70 methylation suppresses apoptosis. Cell Rep 39(6):110794 |
| abstractText | The mammalian KU70 is a pleiotropic protein functioning in DNA repair and cytoplasmic suppression of apoptosis. We report a regulatory mechanism by which KU70's cytoplasmic function is enabled due to a methylation at K570 of KU70 by SET-domain-containing protein 4 (SETD4). While SETD4 silencing reduces the level of methylated KU70, over-expression of SETD4 enhances methylation of KU70. Mutations of Y272 and Y284 of SETD4 abrogate methylation of KU70. Although SETD4 is predominantly a nuclear protein, the methylated KU70 is enriched in the cytoplasm. SETD4 knockdown enhances staurosporine (STS)-induced apoptosis and cell killing. Over-expression of the wild-type (WT) SETD4, but not the SETD4-Y272/Y284F mutant, suppresses STS-induced apoptosis. The KU70-K570R (mouse Ku70-K568R) mutation dampens the anti-apoptosis activity of KU70. Our study identifies KU70 as a non-histone substrate of SETD4, discovers a post-translational modification of KU70, and uncovers a role for SETD4 and KU70-K570 methylation in the suppression of apoptosis. |
