| First Author | Mustafa N | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 1 | PubMed ID | 35008734 |
| Mgi Jnum | J:317688 | Mgi Id | MGI:6853604 |
| Doi | 10.3390/ijms23010311 | Citation | Mustafa N, et al. (2021) E2f2 Attenuates Apoptosis of Activated T Lymphocytes and Protects from Immune-Mediated Injury through Repression of Fas and FasL. Int J Mol Sci 23(1) |
| abstractText | Targeted disruption of E2f2 in mice causes T-cell hyperactivation and a disproportionate cell cycle entry upon stimulation. However, E2f2(-/-) mice do not develop a lymphoproliferative condition. We report that E2f2 plays a Fas-dependent anti-apoptotic function in vitro and in vivo. TCR-stimulated murine E2f2(-/-) T cells overexpress the proapoptotic genes Fas and FasL and exhibit enhanced apoptosis, which is prevented by treatment with neutralizing anti-FasL antibodies. p53 pathway is activated in TCR-stimulated E2f2(-/-) lymphocytes, but targeted disruption of p53 in E2f2(-/-) mice does not abrogate Fas/FasL expression or apoptosis, implying a p53-independent apoptotic mechanism. We show that E2f2 is recruited to Fas and FasL gene promoters to repress their expression. in vivo, E2f2(-/-) mice are prone to develop immune-mediated liver injury owing to an aberrant lymphoid Fas/FasL activation. Taken together, our results suggest that E2f2-dependent inhibition of Fas/FasL pathway may play a direct role in limiting the development of immune-mediated pathologies. |
