| First Author | Barradas M | Year | 2009 |
| Journal | Genes Dev | Volume | 23 |
| Issue | 10 | Pages | 1177-82 |
| PubMed ID | 19451218 | Mgi Jnum | J:148468 |
| Mgi Id | MGI:3845413 | Doi | 10.1101/gad.511109 |
| Citation | Barradas M, et al. (2009) Histone demethylase JMJD3 contributes to epigenetic control of INK4a/ARF by oncogenic RAS. Genes Dev 23(10):1177-82 |
| abstractText | The INK4a/ARF tumor suppressor locus, a key executor of cellular senescence, is regulated by members of the Polycomb group (PcG) of transcriptional repressors. Here we show that signaling from oncogenic RAS overrides PcG-mediated repression of INK4a by activating the H3K27 demethylase JMJD3 and down-regulating the methyltransferase EZH2. In human fibroblasts, JMJD3 activates INK4a, but not ARF, and causes p16(INK4a)-dependent arrest. In mouse embryo fibroblasts, Jmjd3 activates both Ink4a and Arf and elicits a p53-dependent arrest, echoing the effects of RAS in this system. Our findings directly implicate JMJD3 in the regulation of INK4a/ARF during oncogene-induced senescence and suggest that JMJD3 has the capacity to act as a tumor suppressor. |
