What does caspase-8 do in apoptosis?
Therefore, caspase-8 represents the molecular switch that controls apoptosis, necroptosis and pyroptosis, and prevents tissue damage during embryonic development and adulthood.
What role does caspase-8 perform in the cell?
Initially discovered as an initiator protease in apoptosis mediated by death receptors, caspase-8 is now known to have an apparently confounding opposing effect in securing cell survival. It is required to allow mouse embryo survival, and the survival of hematopoietic cells during their development and activation.
Is caspase-8 extrinsic pathway?
Caspase-8 (CASP8) is a cysteine protease that plays a pivotal role in the extrinsic apoptotic signaling pathway via death receptors. The kinetics, dynamics, and selectivity with which the pathway transmits apoptotic signals to downstream molecules upon CASP8 activation are not fully understood.
What starts the extrinsic pathway of blood clotting?
The extrinsic pathway is clinically measured as the prothrombin time (PT). This pathway begins at factor X which is activated to factor Xa. The process of activating factor Xa is a complicated reaction. Tenase is the complex that cleaves factor X into factor Xa.
How does caspase-8 induce apoptosis?
Apoptosis occurs through a tightly regulated cascade of caspase activation. In the context of extrinsic apoptosis, caspase-8 is activated by dimerization inside a death receptor complex, cleaved by auto-proteolysis and subsequently released into the cytosol.
Is caspase-9 intrinsic or extrinsic?
As the most intensively studied initiator caspase, caspase-9 is a key player in the intrinsic or mitochondrial pathway which is involved in various stimuli, including chemotherapies, stress agents and radiation.
What is the substrate of caspase-8?
An important substrate of caspase-8 is RIP, the cleavage of which impairs NF-κB survival signaling (Lin et al., 1999; Martinon et al., 2000). RIP is cleaved by caspase-8 during TNF-R1 and CD95-mediated apoptosis at LQLD (324), separating the N-terminal kinase from the C-terminal death domain (Figure 2a).
What is extrinsic pathway?
The extrinsic pathway consists of the transmembrane receptor tissue factor (TF) and plasma factor VII/VIIa (FVII/FVIIa), and the intrinsic pathway consists of plasma FXI, FIX, and FVIII. Under physiological conditions, TF is constitutively expressed by adventitial cells surrounding blood vessels and initiates clotting.
What is the extrinsic pathway?
The extrinsic pathway is generally the first pathway activated in the coagulation process and is stimulated in response to a protein called tissue factor, which is expressed by cells that are normally found external to blood vessels.
Why is extrinsic pathway called extrinsic?
The pathway of blood coagulation activated by tissue factor, a protein extrinsic to blood, is known as the extrinsic pathway (Figure 1). Tissue factor serves as a cofactor with factor VII to facilitate the activation of factor X. Alternatively, factor VII can activate factor IX, which, in turn, can activate factor X.
What is extrinsic apoptotic pathway?
The extrinsic pathway of apoptosis begins outside a cell, when conditions in the extracellular environment determine that a cell must die. The intrinsic pathway of apoptosis pathway begins when an injury occurs within the cell and the resulting stress activates the apoptotic pathway.
What is extrinsic apoptosis?
What is the role of caspase 8 in the extrinsic death pathway?
Activated caspase-8 can directly stimulate caspase-3 activity (extrinsic death pathway) but can also participate in the activation of the intrinsic death pathway by cleaving Bid. Once cleaved, Bid promotes the release of mitochondrial pro-apoptotic factors leading to the activation of caspase-9 Budihardjo et al (1999).
How is caspase-8 synthesized?
Like all caspases, caspase-8 is synthesized as an inactive single polypeptide chain zymogen procaspase and is activated by proteolytic cleavage, through either autoactivation after recruitment … Caspase-8 is a member of the cysteine proteases, which are implicated in apoptosis and cytokine processing.
Is caspase-8 a proapoptotic protease?
The clinical phenotype of CEDS patients represented a paradox since caspase-8 was considered to be chiefly a proapoptotic protease, that was mainly involved in signal transduction from Tumor necrosis factor receptor family death receptors such as Fas.
What is the role of caspase 8 in the pathogenesis of brain injury?
Krajewska M, et al. Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity. PLoS One. 2011;6:e24341.
