Differential regulation of nuclear and mitochondrial Bcl-2 in T cell apoptosis.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
Activated T cells require anti-apoptotic cytokines for their survival. The anti-apoptotic effects of these factors are mediated by their influence on the balance of expression and localisation of pro- and anti-apoptotic members of the Bcl-2 family. Among the anti-apoptotic Bcl-2 family members, the expression level of Bcl-2 itself and its interaction with the pro-apoptotic protein Bim are now regarded as crucial for the regulation of survival in activated T cells. We studied the changes in Bcl-2 levels and its subcellular distribution in relation to mitochondrial depolarisation and caspase activation in survival factor deprived T cells. Intriguingly, the total Bcl-2 level appeared to remain stable, even after caspase 3 activation indicated entry into the execution phase of apoptosis. However, cell fractionation experiments showed that while the dominant nuclear pool of Bcl-2 remained stable during apoptosis, the level of the smaller mitochondrial pool was rapidly downregulated. Signals induced by anti-apoptotic cytokines continuously replenish the mitochondrial pool, but nuclear Bcl-2 is independent of such signals. Mitochondrial Bcl-2 is lost rapidly by a caspase independent mechanism in the absence of survival factors, in contrast only a small proportion of the nuclear pool of Bcl-2 is lost during the execution phase and this loss is a caspase dependent process. We conclude that these two intracellular pools of Bcl-2 are regulated through different mechanisms and only the cytokine-mediated regulation of the mitochondrial pool is relevant to the control of the initiation of apoptosis.
Scheel-Toellner, D., Raza, K., Assi, L., Pilling, D., Ross, E. J., Lee, W. Y., ... Salmon, M.
citation count
8
complete list of authors
Scheel-Toellner, Dagmar||Raza, Karim||Assi, Lakhvir||Pilling, Darrell||Ross, Emma J||Lee, Wing Yiu||Curnow, S John||Buckley, Christopher D||Akbar, Arne N||Lord, Janet M||Salmon, Mike
