@article{MurtiFenderGlatzleetal.2023, author = {Murti, Krisna and Fender, Hendrik and Glatzle, Carolin and Wismer, Rhoda and Sampere-Birlanga, Salvador and Wild, Vanessa and Muhammad, Khalid and Rosenwald, Andreas and Serfling, Edgar and Avots, Andris}, title = {Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells}, series = {Frontiers in Oncology}, volume = {13}, journal = {Frontiers in Oncology}, doi = {10.3389/fonc.2023.1205788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323103}, year = {2023}, abstract = {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.}, language = {en} }