Apoptosis Flashcards

1
Q

Some characteristics of apoptosis include loss of __ to neighboring cells, fragmentation of ___, and rapid engulfment of dying cell by ___.

A

adhesion.

DNA.

macrophages.

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2
Q

What are some cases, types of cells, where apoptosis is important?

A

abnormal cells, eliminating lymphocytes after ingesting microbes, keep organs the same size (liver), cells with DNA damage.

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3
Q

When you run a gel of an apoptotic cell, you get fragments of DNA separated by ___. This protein, ___, is released from the mitochondria and serves as a marker of apoptosis. Cleavages occur in ___ regions of nucleosomes.

A

size.

cytochrome c

linker.

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4
Q

Activation of caspases is a key event in ___. Caspase stands for ___. This amino acid, ___, is found in the active site of caspases.

Caspases target proteins and cleave them where this amino acid, ___, is found.

A

Apoptosis.

Cysteine aspartyl specific protease.

Cysteine.

Aspartic acid.

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5
Q

Caspases first start as an inactive ___, which is then activated by ___ and other __ caspases.

A

procaspase.

protease cleavage.

active.

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6
Q

There are two major classes of caspases. What are they and what are their functions?

List some of their downstream effects they have in common.

A

Initiator caspase: initiates apoptosis (caspase-8 and caspase-9).

Executioner Caspases: Destroys actual targets and executes apoptosis (caspase-3)

Common downstream effects: cleave downstream proteins, cleave inactive endonuclease, target cytoskeleton, attacks cell adhesion proteins causing cells to roll up into a ball.

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7
Q

T/F: Caspase cascade is reversible.

T/F: Machinery for apoptosis (caspases) is always in place.

A

False. The caspase cascade is irreversible.

True.

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8
Q

Name the two pathways of apoptosis. Which one is mitochondrial dependent?

A

Intrinsic and Extrinsic pathways.

Intrinsic is mitochondrial dependent.

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9
Q

For the extrinsic pathway of apoptosis, extracellular signals bind to ___ receptors to trigger the extrinsic pathway.

A

Death.

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10
Q

Death receptors are homotrimers of transmembrane proteins containing what 3 domains?

A

extracellular binding domain.

single transmembrane domain.

intracellular death domain.

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11
Q

In the extrinsic pathway, the DISC, which stands for ___, is composed of what parts?

The DISC forms after the initial binding of what protein?

After the initial binding, what protein gets recruited?

What does FADD stand for and what are its components?

A

Death Inducing Signal Complex.

DISC is composed of the Death domain, Death effector domain, and procaspase-8 or 10.

DISC forms after Fas binds to Fas Death receptor.

After Fas binding, the FADD adaptor is recruited.

Fas associated death domain, which consists of the death domain and the death effector domain.

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12
Q

Once the DISC is formed, the procaspases are activated to become __?

Once these caspases are activated, what downstream caspases, aka ___ caspases, become activated?

A

caspase-8 or 10.

caspase-3, aka executioner caspase, is activated downstream after caspase-8/10 become activated.

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13
Q

__ receptors restrain the extrinsic pathway because they have ligand binding domains but no death domain.

T/F: These receptors do NOT activate apoptosis.

A

Decoy.

True.

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14
Q

Another extrinsic pathway inhibitor is ___, a protein resembling initiator procaspase, acting as a competitive inhibitor against procaspase-8/10.

Does this protein contain a proteolytic domain?

A

FLIP.

FLIP does not contain a proteolytic domain.

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15
Q

For the ___ pathway, where cells can activate apoptosis from inside the cell, the translocation of __ from the mitochondria is the key event.

Once that protein is released into the cytosol, it will bind to adaptor proteins to activate ___.

A

intrinsic

cytochrome c

procaspase.

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16
Q

cytochrome c binds to ___, which is a procaspase-activating adaptor protein, forming an apoptosome, which activates caspase-_, which then activates downstream executioner caspases such as caspase-_.

A

Apaf1

caspase-9.

caspase-3.

17
Q

The apoptosome is a seven-star structure, that is the combination of what two proteins?

A

Apaf1 and cyt c.

18
Q

What does “Bcl” stand for in the Bcl2 protein?

There are two types of Bcl2 proteins? What are they and how do they function?

A

“B cell lymphoma.”

Pro-apoptotic: promotes release of cytochrome c

Anti-apoptotic: blocks release of cytochrome c (pro-survival)

19
Q

What are the domains of each type of Bcl2 protein?

A

Anti-apoptotic: has 4 domains, BH1-4.

Pro-apoptotic (2 types): BH123 type and BH-3 only type.

20
Q

How does the BH123 protein become activated and what happens when it does?

A

an apoptotic stimulus causes activation of BH123, causing an aggregation of BH123 in the outer mitochondrial membrane, inducing release of cytochrome c.

21
Q

For the anti-apoptotic Bcl2 proteins (Bcl2 and Bcl-XL), how are they anti-apoptotic?

This is part of the __ pathway of apoptosis.

A

They prevent apoptosis by binding to pro-apoptotic proteins (BH123), preventing their aggregation into the active form.

Intrinsic.

22
Q

This protein, ___, inhibits the anti-apoptotic Bcl2 protein, which would normally inhibit the aggregation of BH123 proteins and subsequent release of cyt c.

Therefore, the above protein would be considered pro or anti-apoptotic?

A

BH3.

Pro-apoptotic.

23
Q

IAP stands for ___ and they bind and inhibit ___.

What are two ways that IAPs bind and inhibit their target proteins?

A

Inhibitors of Apoptosis.

caspases.

Two ways: Add ubiquitin to caspases, marking them for destruction. Binding directly to caspases.

24
Q

IAPs are actually good because caspases can undergo ___.

But if there are apoptotic stimuli/signals, then these proteins, ___, are released to block the activity of IAPs and to continue the signaling towards activating the executioner caspases.

A

auto-activation.

anti-IAPs.

25
Q

Since Bcl2 is a(n) ___ of apoptosis, excessive Bcl2 promotes development of cancer.

A

inhibitor.