Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells
Please always quote using this URN: urn:nbn:de:bvb:20-opus-323103
- 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 ofIn 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.…
Author: | Krisna Murti, Hendrik Fender, Carolin Glatzle, Rhoda Wismer, Salvador Sampere-Birlanga, Vanessa Wild, Khalid Muhammad, Andreas Rosenwald, Edgar Serfling, Andris Avots |
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URN: | urn:nbn:de:bvb:20-opus-323103 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Pathologisches Institut |
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken | |
Language: | English |
Parent Title (English): | Frontiers in Oncology |
Year of Completion: | 2023 |
Volume: | 13 |
Article Number: | 1205788 |
Source: | Frontiers in Oncology (2023) 13:1205788. https://doi.org/10.3389/fonc.2023.1205788 |
DOI: | https://doi.org/10.3389/fonc.2023.1205788 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | B cell receptor (BCR); Burkitt lymphoma; Burkitt lymphoma (BL); NFATc1; activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL); apoptosis; cyclosporin A; nuclear localization |
Release Date: | 2024/06/06 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |