Allosteric cross-talk between the hydrophobic cleft and the BH4 domain of Bcl-2 in control of inositol 1,4,5-trisphosphate receptor activity.

ABSTRACT:

Aim

Inositol 1,4,5-trisphosphate receptor (IP₃R) is a ubiquitous calcium (Ca²⁺) channel involved in the regulation of cellular fate and motility. Its modulation by anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) plays an important role in cancer progression. Disrupting this interaction could overcome apoptosis avoidance, one of the hallmarks of cancer, and is, thus, of great interest. Earlier reports have shown the involvement of both the Bcl-2 homology 4 (BH4) and the transmembrane domains (TMDs) of Bcl-2 in regulating IP₃R activity, while the Bcl-2 hydrophobic cleft was associated primarily with its anti-apoptotic and IP₃R-independent action at the mitochondria (Oncotarget. 2016;7:55704-20. doi: 10.18632/oncotarget.11005). The aim of t

SUBMITTER: Shapovalov G 

PROVIDER: S-EPMC9400710 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature