| First Author | Tarcic O | Year | 2016 |
| Journal | Cell Rep | Volume | 14 |
| Issue | 6 | Pages | 1462-1476 |
| PubMed ID | 26854224 | Mgi Jnum | J:268221 |
| Mgi Id | MGI:6204292 | Doi | 10.1016/j.celrep.2016.01.020 |
| Citation | Tarcic O, et al. (2016) RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer. Cell Rep 14(6):1462-1476 |
| abstractText | Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor kappaB (NF-kappaB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-kappaB target genes to augment their transcription. Concordantly, RNF20(+/-) mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. |
