evading apoptosis

Question 1

what is apoptosis

Answer 1

programmed cell death which removes damaged, unwanted or diseased cells. it is highly regulated and does not damage neighbouring cells

Question 2

2 examples of overactive apoptosis

Answer 2

neurodegeneration and immunodeficiency

Question 3

2 examples of underactive apoptosis

Answer 3

cancer and inflammatory conditions

Question 4

physiological use of overactive apoptosis in normal cells

Answer 4

returns cell population to normal after challenge

Question 5

physiological use of underactive apoptosis in normal cells

Answer 5

allows cell accumulation (immune response)

Question 6

what happens to the cell in necrosis

Answer 6

cell swelling, organelle disruption, nuclear swelling and plasma membrane rupture

Question 7

what happens to the cell in apoptosis

Answer 7

cell shrinkage, organelles stay intact, chromatin condensation, plasma membrane integrity is kept

Question 8

cons of necrosis

Answer 8

its messy so cell contents are leaked into surroundings, could cause signal issues

Question 9

how long does it take for apoptosis to occur

Answer 9

30-120 mins

Question 10

3 examples of where messages for intrinsic apoptosis come from

Answer 10

DNA damage, ER stress and hypoxia

Question 11

example of where messages for extrinsic apoptosis come from

Answer 11

death receptors on surface of the cell

Question 12

2 main apoptosis routes

Answer 12

intrinsic and extrinsic

Question 13

where does the message come from in intrinsic apoptosis

Answer 13

inside the cell

Question 14

where does the message come from in extrinsic apoptosis

Answer 14

outside the cell

Question 15

where does the name Caspases derive from

Answer 15

Cysteine ASPartate specific proteASES

Question 16

what do caspases do

Answer 16

cut a specific protein sequence, where they cut is defined by a tetrapeptide

Question 17

what is a tetrapeptide

Answer 17

4 amino acids

Question 18

what are inflammatory caspases responsible for

Answer 18

the maturation of pro-inflammatory cytokines

Question 19

what are initiator caspases responsible for

Answer 19

starting the caspase cascade

Question 20

what are effector caspases responsible for

Answer 20

cleavage of cell substrates and mediate cell killing

Question 21

what are caspases produced as

Answer 21

inactive zymogens

Question 22

how are the inactive zymogens activated

Answer 22

they need to have 2 cleavages

Question 23

what are the different inflammatory caspases

Answer 23

1,4,5,11,12,13 and 14

Question 24

what are the different initiator capsases

Answer 24

2 and 9, 8 and 10

Question 25

what are the different effector/ executioner caspases

Answer 25

3,6 and 7

Question 26

what happens to the initiator caspase as a result of the apototic signal

Answer 26

dimerization, activation and cleavage

Question 27

what does the active initiator caspase do

Answer 27

cleaves the executioner caspase

Question 28

what does the active executioner caspase do

Answer 28

cleaves multiple cell substrates to cause cell death (apoptosis)

Question 29

what do caspases do to cause cell death

Answer 29

they cleave structural proteins and DNA replication/repair enzymes

Question 30

what is ICAD

Answer 30

inhibitor of caspase-activated DNase

Question 31

normal function of PARP and consequence of inactivation

Answer 31

DNA repair, Disabled DNA repair

Question 32

normal function of DNA-RC and consequence of inactivation

Answer 32

DNA rep, halt DNA rep

Question 33

normal function of FAK and consequence of inactivation

Answer 33

regulate cell adhesion, cell detachment/migration

Question 34

normal function of NuMA and consequence of inactivation

Answer 34

nuclear integrity, nuclear disassembly

Question 35

normal function of α-fodrin and actin and consequence of inactivation

Answer 35

cytoskeleton, disassembly of cell structures

Question 36

what does intrinsic apoptosis cause

Answer 36

mitochondrial damage perturbation which causes cytochrome C release

Question 37

what happens in mitochondrial perturbation

Answer 37

the membrane changes and pores form, there is a loss of mitochondrial membrane potential that causes cytochrome C release

Question 38

what happens after Cytochrome C release in intrinsic apoptosis

Answer 38

the messenger binds to inactive APAF-1 and activates it which activates pro-caspase 9

Question 39

what is an apoptosome

Answer 39

an accumulation of APAF-1s

Question 40

What does the Bcl-2 family do

Answer 40

govern mitochondrial permeabilisation, they can promote or inhibit apoptosis

Question 41

what makes a protein part of the Bcl-2 family

Answer 41

all contain Bcl-2 homology domains , its not that they all have the same function

Question 42

2 different types of Bcl-2 proteins

Answer 42

Anti-apoptotic and pro-apoptotic

Question 43

anti-apoptosis Bcl-2 members

Answer 43

essential to life, if you get rid of them then cell populations reduce through apoptosis

Question 44

pro-apoptosis Bcl-2 members: effectors

Answer 44

form pores in mitochondria to release cytochrome C (BAK, BAX)

Question 45

pro-apoptosis Bcl-2 members: BH3

Answer 45

central to life and death decisions of the cell and activation during cell stress will dictate the outcome m

Question 46

when do cell surface receptors transmit a signal in extrinsic apoptosis

Answer 46

once the ligand has bound

Question 46

what happens when the ligand has bound in extrinsic apoptosis

Answer 46

the receptor recruits an adaptor protein which then activates a caspase resulting in a DISC

Question 47

what is a DISC

Answer 47

death inducing signalling complex

Question 48

in extrinsic apoptosis, what family are they receptors part of

Answer 48

Tumour necrosis factor receptor superfamily (TNFR)

Question 49

what does the TNFR superfamily include

Answer 49

TNFR, FAS receptor, TRAIL receptor 1&2

Question 49

what components are the TNFR receptors made of

Answer 49

it has a specific ligand, cytoplasmic region called a death domain (inside cell)

Question 50

what complicates death receptor mediated cell death

Answer 50

decoy receptors

Question 50

what supresses death receptor mediated cell death

Answer 50

FLIP

Question 51

overview of phagocytosis

Answer 51

phagocyte englufs particle for form phagosome for same packaging, anti-inflammatory allows adaptive immune responses to cell derived material, find me eat me signalling

Question 52

Evading apoptosis as a hallmark of cancer, why is it fundamental

Answer 52

cells dont die so they accumulate, they also fail to respond to treatment

Question 53

how cancer evades apoptosis - impaired receptor signalling pathway

Answer 53

reduced expression of death receptors, expression of decoy receptors (no death domain present) or death signals (ligands) so cell doesn't get message to die

Question 54

how cancer evades apoptosis - disrupted balance of Bcl-2 family

Answer 54

overexpression of the anti-apoptotic proteins, underexpression of pro-apoptotic proteins (pores on membrane dont form)

Question 55

3 other ways that cancer evades apoptosis

Answer 55

reduced expression of caspases, increase expression of IAPs, defects/mutations in p53

Question 56

what does redundancy mean

Answer 56

theres multiple ways the cancer can take advantage of pathways e.g. in apoptosis, if one way doesn't work it can do the others

Question 57

what happens with p53 loss

Answer 57

there is a reduction in apoptosis caused by cell stress or DNA damage

Question 58

how does p53 effect the Bcl-2 family

Answer 58

induces BH3-only proteins and allows function of effectors (Bax and Bak)