| Autor: |
Krisna Murti, Hendrik Fender, Carolin Glatzle, Rhoda Wismer, Salvador Sampere-Birlanga, Vanessa Wild, Khalid Muhammad, Andreas Rosenwald, Edgar Serfling, Andris Avots |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Oncology, Vol 13 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2234-943X |
| DOI: |
10.3389/fonc.2023.1205788 |
| Popis: |
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-κB 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 Eµ-MYC – induced B cell lymphomas (BCL). Conditional inactivation of the Nfatc1 gene in B cells of Eµ-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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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