Is caspase-9 an initiator caspase?
In most known forms of intrinsic apoptosis, caspase-9 and caspase-3/7 are the initiator and the downstream effector caspases, respectively.
What type of caspase are caspase 8 and 9?
Caspases are present as inactive pro-enzymes that are activated by proteolytic cleavage. Caspases 8, 9 and 3 are situated at pivotal junctions in apoptosis pathways.
What is the role of apoptosome in apoptosis?
Overview: The Role of the Mammalian Apoptosome The apoptosome is a quaternary protein – an enzyme – that forms during apoptosis (or programmed cell death). Its function is not to directly keep cellular homeostasis nor disassemble damaged, infected or cancerous cells.
What makes up the apoptosome?
The apoptosome is a complex composed of cyt c, apoptotic protease activating factor-1 (Apaf-1), and deoxy adenosine triphosphate (dATP).
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 role of caspase-9?
Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating apoptosis. Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other cellular targets.
How does caspase-9 work?
How is Procaspase 9 activated?
Caspase-9 is activated by binding to Apaf-1, a multidomain adapter protein containing an N-terminal caspase recruitment domain (CARD), followed by a nucleotide-binding and oligomerization domain [13–16].
What are the effects of a deficiency in caspase-9?
A deficiency in caspase-9 largely affects the brain and its development. The effects of having a mutation or deficiency in this caspase compared to others is detrimental. The initiating role caspase-9 plays in apoptosis is the cause for the severe effects seen in those with an atypical caspase-9.
What are the substrates of caspase-9?
Substrates of caspase-9 include caspases-3, -6, and -7. Finally, dimerization of cleaved caspase-9 is inhibited by X-linked inhibitor of apoptosis (XIAP). For Research Use Only. Not for use in diagnostic procedures.
Is Akt an allosteric inhibitor of caspase-9?
Akt acts as an allosteric inhibitor of caspase-9 because the site of phosphorylation of serine-196 is far from the catalytic site. The inhibitor affects the dimerization of caspase-9 and causes a conformational change that affects the substrate-binding cleft of caspase-9.
How do you detect caspase-9 with FITC?
Fluorescein (FITC)-conjugated LEHD-FMK, a specific inhibitor of caspase-9, is utilized in this assay for detection. This reagent is cell permeable, non-toxic and irreversibly binds to the active enzyme. Detection of the labeled cells can be determined by flow cytometry, fluorescent microscopy or a fluorescent plate reader.