| First Author | Espinosa L | Year | 2010 |
| Journal | Cancer Cell | Volume | 18 |
| Issue | 3 | Pages | 268-81 |
| PubMed ID | 20832754 | Mgi Jnum | J:164199 |
| Mgi Id | MGI:4830896 | Doi | 10.1016/j.ccr.2010.08.006 |
| Citation | Espinosa L, et al. (2010) The Notch/Hes1 pathway sustains NF-kappaB activation through CYLD repression in T cell leukemia. Cancer Cell 18(3):268-81 |
| abstractText | It was previously shown that the NF-kappaB pathway is downstream of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL). Here, we visualize Notch-induced NF-kappaB activation using both human T-ALL cell lines and animal models. We demonstrate that Hes1, a canonical Notch target and transcriptional repressor, is responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by repressing the deubiquitinase CYLD, a negative IKK complex regulator. CYLD expression was found to be significantly suppressed in primary T-ALL. Finally, we demonstrate that IKK inhibition is a promising option for the targeted therapy of T-ALL as specific suppression of IKK expression and function affected both the survival of human T-ALL cells and the maintenance of the disease in vivo. |
