What does caspase-9 do in apoptosis?

What does caspase-9 do in apoptosis?

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 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 is a Procaspase?

From The School of Biomedical Sciences Wiki. Procaspases are the inactive precursors to caspases. They are activated by cleaving one or two specific aspartic acids. The procaspase is split into two subunits that form a dimer. Two of these dimers combine to form the activated tetramer that is a caspase.

Does cytochrome c activate caspase-9?

Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells. Cell Death Differ.

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.

Which caspase play vital role in final phase of apoptosis?

Recent work, reviewed here, has revealed that caspase-3 is important for cell death in a remarkable tissue-, cell type- or death stimulus-specific manner, and is essential for some of the characteristic changes in cell morphology and certain biochemical events associated with the execution and completion of apoptosis.

How does apoptosome activate caspase?

Mammalian intrinsic apoptosis requires activation of the initiator caspase-9, which then cleaves and activates the effector caspases to execute cell killing. The heptameric Apaf-1 apoptosome is indispensable for caspase-9 activation by together forming a holoenzyme.

What is the difference between a Procaspase and a caspase?

The key difference between caspase and procaspase is that caspase is an active protease enzyme that is essential in apoptosis or programmed cell death, while procaspase is an inactive protease enzyme that is an inactive precursor of caspase.

How is Procaspase activated?

All caspases are synthesized in cells as catalytically inactive zymogens, and must undergo an activation process. The activation of an effector caspase, such as caspase-3 or -7, is performed by an initiator caspase, such as caspase-9, through an internal cleavage to separate the large and small subunits.

What is apoptosome made of?

The apoptosome is a complex composed of cyt c, apoptotic protease activating factor-1 (Apaf-1), and deoxy adenosine triphosphate (dATP).

What is Fas associated death domain?

Fas-associated death domain (FADD) is an adapter protein that is recruited to the death-inducing signaling complex (DISC) during signaling via death receptors. FADD is a common conduit in both CD95-mediated and TNF-R-mediated apoptosis.

What is FAS in apoptosis?

Fas is a membrane protein belonging to the death receptor family. Cross-linking of Fas by its ligand, FasL, or agonistic anti-Fas antibodies, induces apoptosis of cells expressing Fas on the membrane by triggering a cascade of caspases.

What is the difference between caspase-9β and caspases-9s?

Caspase-9S doesn’t have central catalytic domain, therefore it functions as an inhibitor of caspase-9α by attaching to the apoptosome, suppressing the caspase enzyme cascade and apoptosis. Caspase-9β is referred to as the endogenous dominant-negative isoform.

What is the process of Apaf-1 and pro-caspase-9?

Processing occurs when the apoptosome binds to pro-caspase-9 as apaf-1 assists in the autoproteolytic processing of the zymogen. The processed caspase-9 stays bound to the apoptosome complex, forming a holoenzyme.

How is the pro-domain of caspase-9 linked to the catalytic domain?

The pro-domain is linked to the catalytic domain by a linker loop. The caspase-9 monomer consists of one large and one small subunit, both comprising the catalytic domain.

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.