| First Author | Leal-Sanchez J | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 4 | Pages | 795-806 |
| PubMed ID | 17082815 | Mgi Jnum | J:134830 |
| Mgi Id | MGI:3789861 | Doi | 10.1038/sj.cdd.4402056 |
| Citation | Leal-Sanchez J, et al. (2007) Requirement for Daxx in mature T-cell proliferation and activation. Cell Death Differ 14(4):795-806 |
| abstractText | The protein Daxx promotes Fas-mediated cell death through activation of apoptosis signal-regulating kinase 1, leading to the activation of the MAPKs JNK and p38. Owing to the in utero lethality of daxx-deficient mice, the in vivo role of Daxx has been so far difficult to analyze. We have generated transgenic mice expressing a dominant-negative form of Daxx (Daxx-DN) in the T-cell lineage. We show that Daxx is recruited to the Fas receptor upon FasL engagement and that Daxx-DN expression protects activated T cells from Fas-induced cell death, by preventing the death-inducing signal complex to be properly formed. Normal lymphocyte development and homeostasis are nevertheless observed. Interestingly, we report that both in vitro and in vivo stimulation of Daxx-DN T-lymphocytes leads to increased proliferative T-cell responses. This increased proliferation is associated with a marked increase in tyrosine phosphorylation of LAT and ZAP70 as Daxx-DN favor their recruitment to the T-cell receptor (TCR) complex. These findings identify Daxx as a critical regulator of T-lymphocyte homeostasis by decreasing TCR-induced cell proliferation and by promoting Fas-mediated cell death. |
