Apoptosis Flashcards

1
Q

What occurs during apoptosis?

A

Irreversible once started

Chromatin and nucleus fragments

Cytoskeleton breaks up

Cell shrinks and breaks up into membrane-enclosed fragments

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2
Q

What is the role of phosphatidylserine in apoptosis?

A

Flipped to outer leaflet during apoptosis

Recognized by macrophages for phagocytosis

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3
Q

What are caspases?

A

Protease that is responsible for cleaving many different cell proteins during apoptosis

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4
Q

What are the two types of capsases?

A

Initiator and executioner capsases

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5
Q

What are the targets of capsases?

A

ICAD

Nuclear lamins

Cytoskeletal proteins

Golgi matrix proteins

Scramblase

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6
Q

What are the two main pathways of apoptosis/

A

Intrinsic/Stress

Extrinsic/Death receptors

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7
Q

What are two antiapoptotic proteins?

A

Bcl-2

Bcl-xL

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8
Q

What is the function of Bad and Bid?

A

Proapoptotic proteins that block Bcl-2 and Bcl-xL interaction with pro-apoptotic proteins

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9
Q

What is the function of Bak and Bax?

A

Proapoptotic proteins that translocate to the mitochondria where they are thought to insert in membrane and disrupt its integrity, allowing cytochrome c release

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10
Q

How is the mitochondrial/intrinsic pathway activated?

A

DNA damage or mitchondrial damage causes Apaf-1 and cytochrome c release from the mitochondria to the cytoplasm

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11
Q

What is an apoptosome?

A

Multi subunit complex formed by Apaf-1, cytochrome c, and ATP

Caspase-9 binds to this complex and is activated by autocleavage

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12
Q

What is the function of caspase 9?

A

Proteolytic activation of Caspase-3 and Caspase-7

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13
Q

How is the extrinsic pathway activated?

A

When membrane bound FasL on the surface of one cell binds to Fas receptor on surface of another cell

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14
Q

What occurs when ligand binds to Fas receptor?

A

Fas trimerizes and binds to its adaptor FADD, via death domains at the C-terminal of both proteins

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15
Q

What is the function of FADD?

A

Once it binds to Fas, it binds capsase-8 via death effector domains at its N-terminus

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16
Q

What happens when capsase-8 binds to FADD?

A

Autocleavage and activation of C-8, diffuses to cytoplasm and activates C-3

17
Q

How does Capsase-8 combine the two pathways?

A

Cleaves Bid, which translocates to the mitochondria and disrupts the membrane.

This causes the release of cytochrome c

18
Q

What are five ways apoptosis is regulated?

A

Positive feedback and amplification

Buffers/dampeners

FLIPs

Decoy receptors

p53

19
Q

What is the function of inhibitors-of-apoptosis proteins (IAPs)?

A

bind to procaspases and caspases

20
Q

What is the function of Smac/Diablo?

A

Inhibits IAPs

21
Q

What is the function of FLIPs?

A

compete with caspase-8 for binding to FADD

Lacks catalytic residues

22
Q

What are decoy receptors?

A

Bind to apoptosis-inducing ligand, but cannot transduce apoptotic signal

23
Q

What is the role of p53?

A

Tumpor suppressor protein

Activated via DNa damage

Initiates transcription of pro-apoptotic genes PUMA and Noxa

24
Q

What types of diseases are caused by excessive apoptosis?

A

Neurodegenerative

Immune deficieny

Cardiovascular

Emphysema

AIDS

25
What types of diseases occur with too little apoptosis?
Cancer Autoimmune disease
26
What are two ways cancer cells escape apoptosis?
IAPs expression increased Anti-apoptotic Bcl-2 protein levels increased
27
What are some apoptotic cancer treatment?
BH3 mimetics XIAP antagonists FasL mimetics and Fas activators