Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
Figure 3
Model of survival control by the BCL2 family in physiological and inflammatory conditions. (a) In a physiological context or following an immune response, constitutive or inducible prosurvival proteins (here BCL2) bind multidomain proapoptotic proteins (BAX, BAK) that become unable to oligomerize, thereby resulting in normal cell survival at steady or activated state. (b) In response to intracellular damage, activator BH3-only proteins are induced or activated. They inhibit the prosurvival proteins and activate the effector multidomain proapoptotic proteins, which in turn are homooligomerize, triggering cytochrome release (Cyt c) and apoptosis. Potentially abnormal cells are then eliminated. (c) In a pathological context, such as cancers and chronic inflammatory diseases, prosurvival proteins are upregulated, inhibiting the multidomain and BH3-only proapoptotic proteins. As a result, the membrane of mitochondria remains intact and abnormal cells survive.
(a) At steady state or response to activation signals: BCR, TCR, CD40, proinflammatory cytokines, and so on
(b) Response to intracellular damage signals: growth factor deprivation, stress, UV, viruses, and so on
(c) In cancers or chronic inflammatory disorders: oncogenes, viruses, proinflammatory cytokines, and so on
