Apoptosis

Question 1

what is apoptosis?

Answer 1

programmed cell death brought about by external or internal signals

needed for development into adult forms

Question 2

characteristics of apoptosis

Answer 2

• -cell shrinks
• -loss of CAMS
• -cytoskeleton collapses

Question 3

cytochrome C

Answer 3

released from mito

marker for apoptosis

Question 4

DNA cleavage in apoptosis

Answer 4

cleaved at linker DNA between nucleosomes by endonuclease

Question 5

caspases

Answer 5

proteases that mediate an intracellular proteolytic cascade to cause apoptosis

cysteine in active site

Question 6

caspases target

Answer 6

target proteins and cleave them where Asp acid residues occur

Question 7

procaspases

Answer 7

caspases are first synthesized as these = inactive form

Question 8

activation of procaspases

Answer 8

protease cleaves these

which transforms them into caspases

caspases then also activate procaspases

Question 9

procaspase cleavage

Answer 9

are cleaved at a specific site to create and small and large subunit

which them form a heterodimer w/ a different cleaved procaspase = active caspase

Question 10

2 major caspases

Answer 10

initiator caspase

executioner caspase

Question 11

initiator caspase

Answer 11

–initiates death
–caspase -8 and -10
can self activate

Question 12

executioner caspase

Answer 12

destroys targets to induce death
caspase -3

cleaves downstream proteins, inactive endonuclease, targeting cytoskeleton and CAMs

Question 13

caspase cascade

Answer 13

• -irreversible once started
• -some caspases are needed for life and if gone, fetus will die
• -machinery for apoptosis is always present

Question 14

there are 2 pathways that depend on factors to induce apoptosis

Answer 14

extrinsic path

intrinsic path

Question 15

mito dependence of the 2 pathways

Answer 15

extrinsic - mito independent

intrinsic - dependent

Question 16

extrinsic pathway

Answer 16

death receptors

• -survival factors are removed
• -death signals bind

Question 17

death receptor domains

Answer 17

3 domains

1. extracell binding d
2. TM d
3. intracell death d

receptors are homotrimers - 3 proteins of tumor necrosis family

Question 18

extrinsic pathway cascade

Answer 18

• -Fas binds to Fas death receptor
• -adaptor proteins recruited
• -death domains come together to form DISC
• -caspase -8 and -10 activated
• -downstream executioner activated

Question 19

inhibitory proteins can stop the ____ pathway

Answer 19

extrinsic pathway

Question 20

recruited adaptor proteins - extrinsic pathway

Answer 20

FADD adaptor
procaspase -8 and -10

form trimers
bring death domains together = DISC

Question 21

DISC

Answer 21

death inducing signal complex

Question 22

inhibitory proteins

Answer 22

• -are decoy receptors
• -same as death receptors but no death domain so apoptosis is not induced
• -also includes FLIP protein

Question 23

FLIP

Answer 23

–protein that resembles initiator procaspase but no proteolytic domain

–a competitive inhibitor to oppose procaspase -8 and -10 to prevent apoptosis

Question 24

both types of inhibitory proteins act like?

Answer 24

sponges to absorb the death signals to prevent the start of apoptosis

Question 25

intrinsic pathway

Answer 25

internal inducement of apoptosis due to injury, DNA damage, lack of nutrients mito dependent

Question 26

key event of intrinsic path

Answer 26

translocation of cytochrome C from intermediate space to cytosol

Question 27

release of cytochrome C

Answer 27

- -binds to an adaptor protein Apaf1 - -caspase -9 activated - -executioner caspase activated

Question 28

Apaf1

Answer 28

adaptor protein forms apoptosome which activates caspase -9 which then activates downstream executioner caspase

Question 29

apoptosome

Answer 29

= Apaf1 + cytochrome C

Question 30

final step common to both pathways

Answer 30

activation of downstream executioner caspase caspase -3

Question 31

Bcl2 protein family

Answer 31

- -controls release of cytochrome C into cytosol | - -3 types of this: pro and anti apoptotic

Question 32

pro-apoptotic Bcl2

Answer 32

blocks release of cytochrome C has 3 domains or 1 BH123 or BH3

Question 33

anti-apoptotic Bcl2

Answer 33

promotes release of cytochrome C has 4 distinct domains BH1234 which is also just called Bcl2

Question 34

BH123 activation

Answer 34

- -pro apoptotic - -apoptosis is triggered - -this activates BH123

Question 35

BH123 function

Answer 35

forms aggregation in mito outer membrane induces release of cytochrome C thus inducing intrinsic pathway

Question 36

BH3

Answer 36

pro-apoptotic located in cytosol apoptotic signals activate it which causes it to translocate to mitochondria

Question 37

BH3 function

Answer 37

inhibits the anti-apoptotic Bcl2 proteins thus allowing BH123 to do its function

Question 38

Bcl2

Answer 38

or BH1234 anti-apoptotic includes Bcl2 & Bcl-XL located on cytosolic side of outer mito memb.

Question 39

Bcl2 function

Answer 39

prevent apoptosis by binding to BH123 thus preventing aggregation

Question 40

IAPs

Answer 40

inhibitors of apoptosis bind and inhibit caspases some can add ubiquitin these are necessary because some caspases are self-activating

Question 41

Anti-IAPs

Answer 41

when real apoptotic signals are received --these will stop IAPs from inhibiting caspase activity they release from mito

Question 42

excessive Bcl2 production

Answer 42

- -related to lymphoma - -Bcl2 inhibits apoptosis - -if in excess cell can never die

Question 43

relate excessive Bcl2 protein and p53 mutations

Answer 43

in excess Bcl2 -- cells will not die thus cells w/ DNA damage will continue to live and divide p53 gene stops cell cycles when DNA damage is detected

Question 44

excessive apoptosis is found in ?

Answer 44

heart attacks and stroke