| First Author | Katlinskaya YV | Year | 2016 |
| Journal | Mol Cell Biol | Volume | 36 |
| Issue | 7 | Pages | 1124-35 |
| PubMed ID | 26811327 | Mgi Jnum | J:236199 |
| Mgi Id | MGI:5805349 | Doi | 10.1128/MCB.00988-15 |
| Citation | Katlinskaya YV, et al. (2016) Type I Interferons Control Proliferation and Function of the Intestinal Epithelium. Mol Cell Biol 36(7):1124-35 |
| abstractText | Wnt pathway-driven proliferation and renewal of the intestinal epithelium must be tightly controlled to prevent development of cancer and barrier dysfunction. Although type I interferons (IFN) produced in the gut under the influence of microbiota are known for their antiproliferative effects, the role of these cytokines in regulating intestinal epithelial cell renewal is largely unknown. Here we report a novel role for IFN in the context of intestinal knockout of casein kinase 1alpha (CK1alpha), which controls the ubiquitination and degradation of both beta-catenin and the IFNAR1 chain of the IFN receptor. Ablation of CK1alpha leads to the activation of both beta-catenin and IFN pathways and prevents the unlimited proliferation of intestinal epithelial cells despite constitutive beta-catenin activity. IFN signaling contributes to the activation of the p53 pathway and the appearance of apoptotic and senescence markers in the CK1alpha-deficient gut. Concurrent genetic ablation of CK1alpha and IFNAR1 leads to intestinal hyperplasia, robust attenuation of apoptosis, and rapid and lethal loss of barrier function. These data indicate that IFN play an important role in controlling the proliferation and function of the intestinal epithelium in the context of beta-catenin activation. |
