Caspase-3/Sandbox: Difference between revisions

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In the intrinsic pathway, stimuli such as trophic factor withdrawal, UV irradiation, chemotherapeutics, DNA damage, endoplasmic reticulum (ER) stress, activates B cell lymphoma 2 (BCL-2) homology 3 (BH3)-only proteins like Bim or Bad, leading to BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK) activation and mitochondrial outer membrane permeabilization (MOMP). Following MOMP, cytochrome c is released and binds apoptotic protease-activating factor 1 (APAF1), inducing recruitment of the apoptosome and activation of caspase-9, an initiator caspase. Caspase-9 cleaves and activates effector caspases, caspase-3 and caspase-7, leading to apoptosis through cleavage of death substrates such as Inhibitor of Caspase-activated Deoxyribonuclease (ICAD) and Poly ADP ribose polymerase (PARP). Mitochondrial release of second mitochondria-derived activator of caspase (Smac/DIABLO) relieves the caspase inhibitory function of X-linked inhibitor of apoptosis protein (XIAP).

The extrinsic apoptotic pathway is initiated by the activation of death receptors, such as Fas by FasL. Fas-associated death domain protein (FADD) is recruited to the receptor along with caspase-8. This results in the dimerization and activation of caspase-8, which can then directly cleave and activate caspase-3 and caspase-7, leading to apoptosis.

The extrinsic apoptotic pathway is initiated by the activation of death receptors, such as Fas by FasL. Fas-associated death domain protein (FADD) is recruited to the receptor along with caspase-8. This results in the dimerization and activation of caspase-8, which can then directly cleave and activate caspase-3 and caspase-7, leading to apoptosis. Crosstalk between the extrinsic and intrinsic pathways occurs through BH3-only protein BH3-interacting domain death agonist (BID) cleavage to truncated BID (tBID) by active caspase-8 (Li, Zhu et al. 1998). It has become appreciated more recently that caspase activity, specifically caspase-8, is also required for T cell growth (Alam, Cohen et al. 1999; Kennedy, Kataoka et al. 1999; Misra, Jelley-Gibbs et al. 2005), and that the location and level of active caspases within cells may be a key determinant of survival or death (Misra, Russell et al. 2007; Koenig, Russell et al. 2008). Murine αβ T cells bearing high levels of caspase activity manifest increased rates of both cell growth and cell death (Dohrman, Russell et al. 2005).

Crosstalk between the extrinsic and intrinsic pathways occurs through ~~caspase-8 cleavage and activation of the~~ BH3-only protein BH3-interacting domain death agonist (BID)~~, the product of which (~~truncated BID; tBID) ~~is required in some cell types for death receptor~~-~~induced apoptosis~~ (Li, Zhu et al. 1998). It has become appreciated more recently that caspase activity, specifically caspase-8, is also required for T cell growth (Alam, Cohen et al. 1999; Kennedy, Kataoka et al. 1999; Misra, Jelley-Gibbs et al. 2005), and that the location and level of active caspases within cells may be a key determinant of survival or death (Misra, Russell et al. 2007; Koenig, Russell et al. 2008). Murine αβ T cells bearing high levels of caspase activity manifest increased rates of both cell growth and cell death (Dohrman, Russell et al. 2005).

====Caspase-3====

Caspase-3/Sandbox: Difference between revisions

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 In the intrinsic pathway, stimuli such as trophic factor withdrawal, UV irradiation, chemotherapeutics, DNA damage, endoplasmic reticulum (ER) stress, activates B cell lymphoma 2 (BCL-2) homology 3 (BH3)-only proteins like Bim or Bad, leading to BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK) activation and mitochondrial outer membrane permeabilization (MOMP). Following MOMP, cytochrome c is released and binds apoptotic protease-activating factor 1 (APAF1), inducing recruitment of the apoptosome and activation of caspase-9, an initiator caspase. Caspase-9 cleaves and activates effector caspases, caspase-3 and caspase-7, leading to apoptosis through cleavage of death substrates such as Inhibitor of Caspase-activated Deoxyribonuclease (ICAD) and Poly ADP ribose polymerase (PARP). Mitochondrial release of second mitochondria-derived activator of caspase (Smac/DIABLO) relieves the caspase inhibitory function of X-linked inhibitor of apoptosis protein (XIAP).
-The extrinsic apoptotic pathway is initiated by the activation of death receptors, such as Fas by FasL. Fas-associated death domain protein (FADD) is recruited to the receptor along with caspase-8. This results in the dimerization and activation of caspase-8, which can then directly cleave and activate caspase-3 and caspase-7, leading to apoptosis.
+The extrinsic apoptotic pathway is initiated by the activation of death receptors, such as Fas by FasL. Fas-associated death domain protein (FADD) is recruited to the receptor along with caspase-8. This results in the dimerization and activation of caspase-8, which can then directly cleave and activate caspase-3 and caspase-7, leading to apoptosis. Crosstalk between the extrinsic and intrinsic pathways occurs through BH3-only protein BH3-interacting domain death agonist (BID) cleavage to truncated BID (tBID) by active caspase-8 (Li, Zhu et al. 1998). It has become appreciated more recently that caspase activity, specifically caspase-8, is also required for T cell growth (Alam, Cohen et al. 1999; Kennedy, Kataoka et al. 1999; Misra, Jelley-Gibbs et al. 2005), and that the location and level of active caspases within cells may be a key determinant of survival or death (Misra, Russell et al. 2007; Koenig, Russell et al. 2008).  Murine αβ T cells bearing high levels of caspase activity manifest increased rates of both cell growth and cell death (Dohrman, Russell et al. 2005).
-Crosstalk between the extrinsic and intrinsic pathways occurs through caspase-8 cleavage and activation of the BH3-only protein BH3-interacting domain death agonist (BID), the product of which (truncated BID; tBID) is required in some cell types for death receptor-induced apoptosis (Li, Zhu et al. 1998). It has become appreciated more recently that caspase activity, specifically caspase-8, is also required for T cell growth (Alam, Cohen et al. 1999; Kennedy, Kataoka et al. 1999; Misra, Jelley-Gibbs et al. 2005), and that the location and level of active caspases within cells may be a key determinant of survival or death (Misra, Russell et al. 2007; Koenig, Russell et al. 2008).  Murine αβ T cells bearing high levels of caspase activity manifest increased rates of both cell growth and cell death (Dohrman, Russell et al. 2005).
 ====Caspase-3====