Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2 MCD Cancer > cell cycle > Flashcards

cell cycle Flashcards

apoptosis: explain the difference between necrosis and apoptosis, recall cellular mechanisms which execute the apoptotic response, and recall how the Bcl-2 family proteins can modulate apoptosis

1
Q

5 reasons for apoptosis (programmed cell death)

A

harmful cells, developmentally defective cells, excess/unnecessary cells, obsolete cells, exploitation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

technique for labelling apoptotic cells, and how does it work

A

tunel technique, as it labels fragments of DNA (nucleus in yellow)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

define necrosis

A

unregulated cell death association with trauma, cellular disruption and an inflammatory response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

define apoptosis

A

regulated cell death; controlled disassembly of cellular contents without disruption (no inflammatory response)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

stages of necrosis

A

plasma mebrane becomes permeable -> cell swelling and rupture of cellular membranes -> release of proteases leading to autodigestion and dissolution of cell -> localised inflammation as phagocytic cells clear up debris (healthy cells either side divide to fill gap)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

2 phases of apoptosis

A

latent and execution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what happens in latent apoptosis

A

death pathways activated, but cells appear morphologically the same

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

7 stages of execution phase

A

loss of microvilli and intercellular junctions -> cell shrinkage -> loss of plasma membrane asymmetry (phosphatidylserine lipid appears in outer leaflet, as imbalance in lipid composition) -> chromatin and nuclear condensation -> DNA fragmentation -> formation of membrane blebs -> fragmentation into membrane-enclosed apoptotic bodies -> apoptotic bodies phagocytosed by neighbouring cells and macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what happens during apoptosis to ensure no inflammation

A

plasma membrane remains intact

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

DNA modification in apoptosis

A

DNA fragments, leading to more “ends” which are labelled by adding an extra fluorescently-tagged base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

4 types of cell death (graded response)

A

necrosis, apoptosis, apoptosis-like PCD, necrosis-like PCD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is apoptosis-like programmed cell death

A

some (but not all) features of apoptosis, with a display of phagocytic recognition molecules before plasma membrane lysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is necrosis-like programmed cell death

A

variable features of apoptosis before cell lysis (aborted apoptosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

4 mechanisms of apoptotic cell death

A

executioners -> initiating death programme -> Bcl-2 family -> stopping death programme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what executes apoptotic cell death

A

caspases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what 2 things initiate death programme

A

death receptors, mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are caspases (full name)

A

cysteine-dependent aspartate-directed proteases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are caspases activated by

A

proteolysis (synthesised in cell as zymogens, but activated by cleavage)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

2 types of caspases

A

initiator (8, 9), effector (3, 7, 6, 2, 1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what prodomains are present in caspases 2 and 9

A

CARD (caspase recruitment domain); also p20, p10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what prodomains are present in caspases 10 and 8

A

DED (death effector domain); also p20, p10

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how do caspases dimerise

A

homotypic protein-protein interactions (dimerise with same caspase), ensuring localisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

effector caspases

A

3, 6, 7 (just p20, p10)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

caspase maturation pathway

A

procaspases (zymogens) -(proteolytic cleavage, releasing inactive prodomains)-> active enzyme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

in the caspase maturation pathway, what is cleavage of inactive procaspase precursor followed by

A

folding of 2 large and 2 small chains to form an active L2S2 heterotetramer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

3 functions of caspase cascades

A

amplification, divergent responses, regulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

function of initiator caspases (8, 9)

A

trigger apoptosis by cleaving and activating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

function of effector caspases (3, 7, 6, 2, 1)

A

carry out apoptotic programme

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

function of caspase 10

A

regulator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

2 things effector caspases do to execute apoptotic programme

A

cleave and inactivate proteins or complexes (e.g. nuclear laminins to cause nuclear breakdown), or activate enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

example of enzyme activated by effector caspases

A

protein kinases and nucleases, such as caspase activated DNase (CAD)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

2 ways effector caspases activate enzymes

A

direct cleavage, cleavage of inhibitory molecules

33
Q

2 mechanisms of caspase activation

A

death by design (receptor-mediated extrinsic pathways), death by default (mitochondrial intrinsic death pathway)

34
Q

death by design (receptor-mediated extrinsic pathways): death receptor stage

A

secreted or transmembrane ligands (trimeric) bind to EC cysteine rich domains (all have IC death domain - DD)

35
Q

death by design (receptor-mediated extrinsic pathways): ligands in apoptosis vs normal

A

trimeric in apoptosis, dimeric when normal

36
Q

death by design (receptor-mediated extrinsic pathways): adapter proteins activation and inhibition

A

activation FADD consists of DED (death effector domain) and DD (death domain); inhibition FLIP consists of 2x DED domains

37
Q

death by design (receptor-mediated extrinsic pathways): what do DD and DED domains bind to

A

similar domains on other proteins

38
Q

death by design (receptor-mediated extrinsic pathways): signalling through death receptors e.g. Fas/Fas-ligand

A

receptor (Fas) trimerisation by death ligand (Fas-L on lymphocyte) -> IC recruitment of adapter protein (FADD) through its DD to DD of Fas -> recruitment and oligomerisation of procaspase 8 through DED to FADD DED -> formation of death-inducing signalling complex (DISC)

39
Q

death by design (receptor-mediated extrinsic pathways): where is Fas upregulated

A

on infected cells

40
Q

death by design (receptor-mediated extrinsic pathways): what does initiator procaspase 8 oligomerisation result in

A

cleavage and activation (initiator procaspase 8 and trimerised receptor tails/FADD) -> active initiator caspase 8 tetramer released from receptor

41
Q

death by design (receptor-mediated extrinsic pathways): 2 types of initiator procaspases catalytic activity

A

some have intrinsic low catalytic activity (oligomerisation allows transcleavage), others activated by conformational change on oligomerisation

42
Q

death by design (receptor-mediated extrinsic pathways): how many procaspases are required to form active tetramer

A

at least 2 (one must cleave the other)

43
Q

-

A

-

44
Q

death by design (receptor-mediated extrinsic pathways): what is death receptor activation of caspase 8 (initiator caspase) inhibited by

A

FLIP (2x DED domains), with long form containing p20 and p10, but short form not having these

45
Q

death by design (receptor-mediated extrinsic pathways): how do FLIP inhibit death receptor activation of procaspase 8

A

no proteolytic activity so competes with procaspase 8 for binding to receptor tails/FADD via DED domains, so incorporates into receptor-procaspase complexes and interferes with transcleavage

46
Q

death by design (receptor-mediated extrinsic pathways): what does caspase 8 (initiator caspase) activate

A

downstream effector caspases

47
Q

death by default (mitochondrial intrinsic death pathway): 4 stages

A

loss of mitochondrial membrane potential (ΔΨ) -> release of cytochrome c -> release of other apoptosis-inducing factors -> formation of apoptosome complex

48
Q

death by default (mitochondrial intrinsic death pathway): what causes a loss of mitochondrial membrane potential, causing release of cytochrome c

A

cellular stresses e.g. lack of/overstimulation by growth factors, DNA damage (p53), ROS

49
Q

what does the apoptosome (wheel of death) contain

A

apaf-1 (apoptotic activating factor-1; contains CARD, ATPase and WD-40 repeats)), cytochrome c, ATP, procaspase 9

50
Q

how many molecules form apoptosome

A

7

51
Q

what domain is at centre of apoptosome

A

CARD (caspase recruitment domain)

52
Q

what domain is at edge of apoptosome

A

WD-40 repeats (protein-protein interactions)

53
Q

what does cytochrome c bind to

A

WD40 repeats

54
Q

what can each apaf-1 in heptameric apoptosome potentially bind to

A

procaspase 9 via CARD domain of apaf-1

55
Q

what does oligomerisation bring together, and what does this result in

A

oligomerisation brings multiple procaspase 9s close together, resulting in cleavage, activation and release as active caspase 9 tetramer

56
Q

what does active caspase 9 tetramer initiate

A

caspase cascade leading to apoptosis

57
Q

what does the apoptosome require, and consequently what determines whether cell death is by necrosis or apoptosis

A

ATP, so if present cell undergoes apoptosis, but if not cell undergoes necrosis

58
Q

what are the principal mechanisms of apoptosis

A

bid links receptor and mitochondrial death pathways

59
Q

principal mechanisms of apoptosis: what does caspase 8 cleave, and what does this enhance (both pathways activated)

A

cleaves Bid which enhances release of mitochondrial proteins, engaging intrinsic pathway (shared effector programmes, with caspase 8 enhancing mitochondrial intrinsic cell death)

60
Q

what are the modulators of apoptosis

A

Bcl-2 family proteins

61
Q

domains of Bcl-2

A

BH4, BH3, BH1, BH2, transmembrane (attached to mitochondrial membrane)

62
Q

2 anti-apoptotic Bcl-2 family proteins

A

Bcl-2, Bcl-xL

63
Q

location of anti-apoptotic Bcl-2 family proteins

A

mitochondria

64
Q

4 pro-apoptotic Bcl-2 family proteins

A

Bid, Bad, Bax, Bak

65
Q

location of pro-apoptotic Bcl-2 family proteins

A

move between cytosol and mitochondria

66
Q

how is growth factor receptor used by PI3’-kinase used for growth

A

growth factor -> binds to growth factor receptor -> Ras -> ERK -> growth

67
Q

PI3’-kinase signalling pathway in cell cycle and apoptosis regulation to ensure survival and proliferation

A

growth factor -> binds to growth factor receptor -> PI3’-K -> PDK-1 -> PKB/Akt -> survival and proliferation

68
Q

PI3’-kinase signalling pathway in cell cycle and apoptosis regulation: what is PI3’-K and what does it do to ensure cell survival

A

lipid kinase involved in growth control and cell survival by activating (phosphorylating) protein kinase PKB/Akt (from PIP2 to PIP3 on membrane), which is anti-apoptotic

69
Q

2 sections of PI3’-kinase

A

p85 (adapter) and p110 (kinase)

70
Q

how does PKB/Akt block apoptosis (4 things)

A

phosphorylates and inactivates Bad and caspase 9, inactivates FOXO transcription factors (promote expression of apoptosis-promoting genes), other e.g. stimulates ribosome production and protein synthesis

71
Q

regulation of apoptosis by Bcl-2 family proteins via BH3 heterodimerisation: cell survival

A

growth factor present causes PKB/Akt production -> in mitochondrial matrix, heterodimers Bcl-2 and Bax inactive by BH3-BH3 domains, and phospho-Bad inactive in cytosol

72
Q

regulation of apoptosis by Bcl-2 family proteins via BH3 heterodimerisation: apoptosis

A

growth factor absent -> in mitochondrial matrix, Bad dephosphorylated and released -> displaces Bcl-2/-xL from Bak -> Bax/Bak pore in mitochondria -> release of cytochrome C

73
Q

what counteracts PI3’-K signalling

A

PTEN (lipid phosphatase)

74
Q

what does PTEN do to counteract PI3’-K signalling

A

reverses PI3’-K catalysed reaction, so dephosphorylates and prevents anti-apoptosis

75
Q

what regulates apoptosis extrinsic pathway

A

inhibitor of apoptosis proteins (IAPs)

76
Q

2 ways inhibitor of apoptosis proteins (IAPs) regulate apoptosis extrinsic pathway

A

bind to procaspases and prevent activation, bind to active caspases and inhibit their activity

77
Q

3 cytoprotective/anti-apoptotic pathways

A

intrinsic pathway (Bcl-2/-xL), extrinsic pathway (FLIP, IAPs), growth factor pathways via PI3’-K and PKB/Akt

78
Q

how do cancer cells avoid apoptosis

A

apoptosis regulators as oncogenes or tumour suppressors

79
Q

2 therapeutic uses of apoptosis

A

harmful (oncogenic) cells (viral infection/DNA damage), chemotherapeutic killing of tumour cells e.g. dexamethasone stimulates DNA cleavage

Y2 MCD Cancer (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions