| First Author | Chaves-Pérez A | Year | 2019 |
| Journal | Science | Volume | 364 |
| Issue | 6443 | PubMed ID | 31147493 |
| Mgi Jnum | J:277739 | Mgi Id | MGI:6316959 |
| Doi | 10.1126/science.aaq1165 | Citation | Chaves-Perez A, et al. (2019) URI is required to maintain intestinal architecture during ionizing radiation. Science 364(6443) |
| abstractText | Ionizing radiation (IR) can cause gastrointestinal syndrome (GIS), a lethal disorder, by means of unknown mechanisms. We show that high-dose irradiation increases unconventional prefoldin RPB5 interactor (URI) levels in mouse intestinal crypt, but organ regeneration correlates with URI reductions. URI overexpression in intestine protects mice from radiation-induced GIS, whereas halving URI expression sensitizes mice to IR. URI specifically inhibits beta-catenin in stem cell-like label-retaining (LR) cells, which are essential for organ regeneration after IR. URI reduction activates beta-catenin-induced c-MYC expression, causing proliferation of and DNA damage to LR cells, rendering them radiosensitive. Therefore, URI labels LR cells which promote tissue regeneration in response to high-dose irradiation, and c-MYC inhibitors could be countermeasures for humans at risk of developing GIS. |
