Constitutive IP₃ signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP₃ receptor disruptor BIRD-2.

ABSTRACT: Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP₃) receptor (IP₃R)-mediated Ca²⁺-signaling. A peptide tool (Bcl-2/IP₃R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP₃Rs by targeting Bcl-2's BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines. Particularly, DLBCL cells with high levels of IP₃R2 were sensitive to BIRD-2. Here, we report that BIRD-2-induced cell death in DLBCL cells does not only depend on high IP₃R2-expression levels, but also o

SUBMITTER: Bittremieux M 

PROVIDER: S-EPMC6370760 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature