| First Author | Murti K | Year | 2023 |
| Journal | Front Oncol | Volume | 13 |
| Pages | 1205788 | PubMed ID | 37546418 |
| Mgi Jnum | J:358411 | Mgi Id | MGI:7780273 |
| Doi | 10.3389/fonc.2023.1205788 | Citation | Murti K, et al. (2023) Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells. Front Oncol 13:1205788 |
| abstractText | In Burkitt lymphoma (BL), a tumor of germinal center B cells, the pro-apoptotic properties of MYC are controlled by tonic B cell receptor (BCR) signals. Since BL cells do not exhibit constitutive NF-kappaB activity, we hypothesized that anti-apoptotic NFATc1 proteins provide a major transcriptional survival signal in BL. Here we show that post-transcriptional mechanisms are responsible for the calcineurin (CN) independent constitutive nuclear over-expression of NFATc1 in BL and Emicro-MYC - induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Emicro-MYC mice leads to apoptosis of BCL cells in vivo and ex vivo. Inhibition of BCR/SYK/BTK/PI3K signals in BL cells results in cytosolic re-location of NFATc1 and apoptosis. Therefore, NFATc1 activity is an integrated part of tonic BCR signaling and an alternative target for therapeutic intervention in BL. |
