Brainscape's Knowledge GenomeTM

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


See full index

Y2 Cancer > Apoptosis > Flashcards

Apoptosis Flashcards

1
Q

What may cause 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

Define necrosis

A

Unregulated cell death associated with trauma, cellular disruption and an inflammatory response

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

Describe the process of necrosis

A
  1. Plasma membrane becomes 2. permeable
    Cell swelling and rupture of cellular membranes
  2. Release of proteases leading to autodigestion and dissolution of the cell
  3. Localised inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What occurs in the latent phase of apoptosis

A

Death pathways are activated, but cells appear morphologically the same

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

What occurs in the execution phase of apoptosis

A

Loss of microvilli, intercellular junctions and plasma membrane asymmetry (phosphatidylserine lipid appears in outer leaflet)
Cell shrinkage
Chromatin and nuclear condensation
DNA fragmentation
Formation of membrane blebs
Fragmentation into membrane-enclosed apoptotic bodies

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

How is the apoptotic body removed

A

Phagocytosis by surrounding cells e.g. macrophages

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

Describe DNA modification in apoptosis can be viewed

A

DNA ladders - fragmentation

TUNEL - DNA fragmentation leads to more ‘ends’, labelled by adding a fluorescently tagged base

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

Define apoptosis-like PCD

A

Some, but not all, features of apoptosis.

Display of phagocytic recognition molecules before plasma membrane lysis

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

Define Necrosis-like PCD

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
11
Q

What are the 4 steps of the apoptotic cell death mechanism

A
  1. Caspases (executioners)
  2. Death receptors and mitochondria
  3. Bcl-2 family
  4. Stopping the death programme
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the full name of caspases

A

Cysteine-dependent aspartate-directed proteases

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

What is the role of caspases in apoptosis

A

Executioners of apoptosis
Activated by proteolysis
Cascade of activation

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

What is the CARD and DED

A

Targeting subunits found on imitator caspases
CARD - Caspase Recruitment Domain
DED - Death Effector Domain

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

What are the initiator caspases and describe their structure

A

Caspase 2, 8, 9 and 10
Have that same pair of subunits, but in addition have an extra TARGETING subunit (protein-protein interacting domain) which directs them to a particular location
DED found on caspase 8 and 10

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

What are the effector caspases and describe their structure formation

A

Caspase 3, 6, and 7
Similar molecular organization
Starts off as a single chain polypeptide with two subunits (large + small) that are released by proteolytic cleavage during maturation

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

Explain the process of caspase maturation

A

Cleavage of the inactive procaspase precursor is followed by 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
18
Q

What are the roles of imitator and effector caspases in the caspase cascade

A

Initiator - trigger apoptosis by cleaving and activating effector caspases

Effector - carry out the apoptotic programme

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

How do effector caspases execute the apoptotic programme

A

Cleave and inactivate proteins or complexes (e.g. nuclear lamins leading to nuclear breakdown)

Activate enzymes by direct cleavage, or cleavage of inhibitory molecules
(incl. protein kinases; nucleases, e.g. Caspase-Activated DNase, CAD)

20
Q

What are the mechanisms of caspase action

A

Death by design – Receptor-mediated (extrinsic) pathways

Death by default – Mitochondrial (intrinsic) death pathway

21
Q

Describe the structure of death receptors

A 
Found on all cells
Consists of: 
Extracellular cysteine- rich domain
Single transcellular domain 
Cytoplasmic tail with a “death domain”
22
Q

When are death receptors activated

A

when they encounter secreted or transmembrane trimeric ligands (eg TNF or Fas) called “DEATH LIGANDS”

23
Q

Which are the two adaptor proteins involved in receptor-mediated apoptosis

A

Activation - FADD

Inhibition - FLIP (allows regulation)

24
Q

Which domains are contained in FADD and FLIP

A

FADD - DED and DD
FLIP - DED x 2
(DED = death effector domain)
(DD= death domain)

25
Q

Describe the process of signalling through death receptors using Fas receptor as an example

A
  1. Receptor (Fas) trimerisation by ligand (Fas-L on lymphocyte)
  2. Recruitment of adapter protein (FADD) through DD
  3. Recruitment and oligomerisation of procaspase 8 through its DED to FADD DED
  4. Formation of the Death-Inducing-Signalling Complex (DISC)
  5. Cross-activation of procaspase8, whereby they cleave each other within the complex (due to close proximity). The active caspase 8 is then released, and it cleaves effector caspases to execute the death programme
26
Q

What is the role of FLIP in death receptor activation of caspase 8

A

Inhibits death receptor activation of caspase 8
No proteolytic activity
Competes with procaspase via DED for binding to receptor tails

27
Q

Describe the mitochondrial regulation of apoptosis

A
  1. Cellular stresses cause loss of mitochondrial
    membrane potential (ΔΨ)
  2. Release of cytochrome c and other apoptosis-
    inducing factors
  3. Formation of the
    apoptosome complex
28
Q

What does the apoptosome contain

A

APAF-1 (apoptotic activating factor 1)
cytochrome C
ATP
procaspase 9

29
Q

Describe the structure of the Apaf-1LC

A

At one end, Apaf1 contains a number of repeats that are involved in protein-protein interactions (WD-40)
At the other end there is an ATPase domain.
At the front there is a caspase recruitment domain (CARD), which is also found in some initiator caspases (e.g. caspase 9)

30
Q

Describe the process of death by default

A
  1. Cytochrome C binds to the WD-40 repeats on Apaf-1
  2. Heptamer (apoptosome) formation, requires ATP
  3. The CARD domains at the centre of the heptamer are capable of interacting with CARD domains on procaspase-9 (7 bind in total)
  4. The close proximity of the procaspase 9s mean they can cross- cleave and activate each other to produce caspase 9.
  5. This is released and is able to trigger the caspase cascade > apoptosis
31
Q

How does energy levels in the cell affect the method of cell death

A

ATP - apoptosis

No ATP - necrosis

32
Q

How is the receptor-mediated pathways distinguished from the mitochondria-mediated when one imitates the other

A

Mitochondria-mediated pathway requires ATP

33
Q

What is Bid and what does it do

A

Protein which links receptor-mediated and mitochondria-mediated pathways together

34
Q

How doe Bid carry out its function

A

Bid is cleaved by caspase
Once it is cleaved, it can go to the mitochondria and
promote the release of cytochrome C, therefore recruiting the mitochondria-mediated pathway

35
Q

Which molecules are involved in modulation/regulation of apoptosis

A

The Bcl-2 Family
Growth Factors
Phosphatidylinositol 3-kinase (PI3-K)
Extrinsic regulators

36
Q

Which domain do all 3 groups of Bcl-2 family proteins contain and what is it function

A

BH3 domain
BH3 is a protein-protein interaction (dimerization) motif that allows proteins of this family to associate and dimerise with each other

37
Q

What are the two categories of Bcl-2 family proteins and where are they found + give examples

A

Anti-apoptotic - localised to the mitochondrial membrane (eg Bcl-2 and Bcl-xL)

Pro-apoptotic - move between the cytosol and the mitochondrial membrane (eg Bid, Bad and Bax)

38
Q

What is Phosphatidylinositol 3-kinase and what is it structure

A

PI3-K is a lipid kinase involved in growth control and cell survival
Has a targeting subunit, and adaptor subunit and a catalytic subunit

39
Q

What is the role of PI3-K

A

Phosphorylates PIP2 to PIP3, which is recognized by the adapter subunit of PKB (protein
kinase B) [also known as Akt]

40
Q

Explain how PKB/Akt induces cell survival by blocking apoptosis

A
  1. PKB is recruited to the cell membrane and is activated, with anti-apoptotic effects
  2. PKB phosphorylates the Bad, and causes it to be help in an inactive heterodimer in the cytoplasm
  3. Other pro-apoptotic proteins (including Bid + Bax) are held in their inactive heterodimers by the BH3 domains of the anti-apoptotic Bcl-2/xL proteins
  4. With the pro-apoptotic proteins held in inactive heterodimers, cell survival and proliferation are promoted
41
Q

What are the other roles of protein kinase B

A

Phosphorylates and inactivates caspase 9
Inactivates FOXO transcription factors (FOXOs promote expression of apoptosis-promoting genes)
Other, e.g. stimulates ribosome production and protein synthesis

42
Q

What is PTEN and what does it do

A

PTEN is a lipid phosphatase that counteracts the production of PKB therefore reducing the regulation of cell survival and promoting apoptosis

43
Q

What are IAPs and what do they do

A

IAPs (inhibitors of apoptosis proteins) regulate programmed cell death by binding to procaspases and preventing their activation, and binding to active caspases and inhibiting their activity.

44
Q

How can cancer cells avoid apoptosis

A

Tumour suppressors (PTEN) are often deleted/inactivated in many cancers
Proto-oncogenes will promote apoptosis
Oncogenes (mutated from proto-oncogenes) are often overexpressed in cancers, eg Bcl-2 and PKB

45
Q

What are the therapeutic uses of apoptosis in cancer

A

Harmful (oncogenic) cells (e.g. cells with viral infection, DNA damage)

Chemotherapeutic killing of tumour cells, e.g. Dexamethasone stimulates DNA cleavage

Y2 Cancer (16 decks)

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