Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells

Murti, Krisna and Fender, Hendrik and Glatzle, Carolin and Wismer, Rhoda and Birlanga, Salvador Sampere and Wild, Vanessa and Muhammad, Khalid and Rosenwald, Andreas and Serfling, Edgar and Avots, Andris (2023) Calcineurin-independent NFATc1 signaling is essential for survival of Burkitt lymphoma cells. Frontiers in Oncology, 13 (120578). pp. 1-10.

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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-kB 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. KEYWORDS apoptosis, Burkitt lymphoma, cyclosporin A, nuclear localization, NFATc1, activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), B cell receptor (BCR), Burkitt lymphoma (BL)

Item Type:	Article
Subjects:	R Medicine > R Medicine (General) > R5-920 Medicine (General)
Divisions:	04-Faculty of Medicine > 11718-Pathology Anatomy (Sp
Depositing User:	dr., Ph.D. Krisna Murti
Date Deposited:	25 Jul 2023 23:35
Last Modified:	25 Jul 2023 23:35
URI:	http://repository.unsri.ac.id/id/eprint/120600

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