| First Author | Ouyang K | Year | 2014 |
| Journal | Nat Commun | Volume | 5 |
| Pages | 4814 | PubMed ID | 25215520 |
| Mgi Jnum | J:252084 | Mgi Id | MGI:6107585 |
| Doi | 10.1038/ncomms5814 | Citation | Ouyang K, et al. (2014) Loss of IP3R-dependent Ca2+ signalling in thymocytes leads to aberrant development and acute lymphoblastic leukemia. Nat Commun 5:4814 |
| abstractText | Calcium ions (Ca(2+)) function as universal second messengers in eukaryotic cells, including immune cells. Ca(2+) is crucial for peripheral T-lymphocyte activation and effector functions, and influences thymocyte selection and motility in the developing thymus. However, the role of Ca(2+) signalling in early T-lymphocyte development is not well understood. Here we show that the inositol triphosphate receptors (IP3Rs) Ca(2+) ion channels are required for proliferation, survival and developmental progression of T-lymphocyte precursors. Our studies indicate that signalling via IP3Rs represses Sox13, an antagonist of the developmentally important transcription factor Tcf-1. In the absence of IP3R-mediated Ca(2+) signalling, repression of key Notch transcriptional targets--including Hes1--fail to occur in post beta-selection thymocytes, and mice develop aggressive T-cell malignancies that resemble human T-cell acute lymphoblastic leukemia (T-ALL). These data indicate that IP3R-mediated Ca(2+) signalling reinforces Tcf-1 activity to both ensure normal development and prevent thymocyte neoplasia. |
