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Flashcards in Apoptosis Deck (47)
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1
Q

programmed cell death (PCD)

A

a sequentially ordered death process, three main types: apoptosis, macro-autophagy, necroptosis

2
Q

apoptosis

A

type 1 PCD, usually associated with suicide of a cell

3
Q

caspases

A

family of cysteinyl aspartate-specific peptidases, that are the effector proteases activated during apoptosis

4
Q

early identifiers of apoptotic cells

A
  • budding of cytoplasmic membrane
  • shrinkage of nuclei
  • chromatin condensation
5
Q

function of apoptosis

A

balance between loss of positive signals and receipt of negative signals

6
Q

role of apoptosis

A
development
killing virus
removing cytotoxic T-cells
aging
maintain homeostasis
7
Q

diseases because apoptosis is INHIBITED

A

cancers: breast, prostate, ovarian
autoimmune
viral infection

8
Q

diseased because apoptosis is INCREASED

A
AIDS
alzheimers
parkinson's
ALS
myelodysplastic syndrome
heart attack, stroke
liver disease via alcohol
9
Q

steps of apoptotic process

A

signal to initation to effectos to execution/degradation to corpse disposal

10
Q

caspase initiators

A

8, 9, 10

11
Q

caspase executioners

A

3, 6, 7

12
Q

activation of caspases generally involves

A

cleavage between the carboxyl and middle domains

13
Q

caspases consist of 3 domains

A
  1. amino terminal
  2. middle large domain
  3. carboxyl terminal
14
Q

pro-executionary caspases exist as

A

dimers

15
Q

initiator pro-caspases exist as

A

monomers

16
Q

caspases differ in lengths of

A

pro-domains

presence/absence of adapter-recognition

17
Q

Major Mechanisms for caspase activation: extrinsic pathway

A

death receptor

18
Q

Major Mechanisms for caspase activation: intrinsic pathway

A

mitochondrial

19
Q

death receptor extrinsic pathway components

A
  • death receptors
  • ligands
  • adapter proteins
  • initiator protease
  • executioner proteases
20
Q

death receptor ligands

A

structurally related members of the tumor necrosis factor family
span the plasma membrane (have extra and inter cellular tails)
anchored to the cell but can be released by proteolytic cleavage

21
Q

death receptors

A

structurally related members of the tumor necrosis factor family
have cysteine-rich extra cellular domains
have cytoplasmic tail that contains a death domain sequence

22
Q

mitochondrial intrinsic pathway

A

does not involve death receptors, changes in mitochondrial fucntion preceded caspase activation with many non death receptor inducers of apoptosis

23
Q

apoptosome

A

functions as a scaffold for RECRUITMENT and ACTIVATION of pro-caspase 9

24
Q

intrinsic apoptotic pathway involves

A
  • receipt of apoptotic signal causes release of cytochrome C
  • cytochrome C binds to Apaf-1 causing the hydrolysis of ATP and partial relaxing of Apaf-1
  • exchange of ATP for bound ADP allows Apaf-1 to fully relax
  • the CARD domains in the apoptosome assume a conformation that enables them to recruit pro-caspase 9 molecules
  • caspase 9 activates executionary pro-caspases 3 and 7
25
Q

what activates the mitochondrial apoptotic pathway

A

anything that will induce the release of cytochrome C

26
Q

agents that cause mitochondrial dysfunction directly

A

target the respiratory chain

target the electrochemical gradient of the inner membrane

27
Q

important concepts regarding mechanism of initiator pro-caspase activation

A
  • involves an adaptor protein
  • recruitment of pro-caspase to the adapter protein is mediated by specific “domain-domain” interactions
  • adapter protein/pro-caspase complexes aggregate/oligomerize and induces conformational change in pro-caspases facilitating activation
28
Q

caspase - 3 =

A

executioinary caspase

29
Q

caspases are activated by

A

specific cleavage after an aspartate residue

30
Q

the whole caspase system is set up into a

A

self-amplifying loop

31
Q

caspases generally have a

A

tetrapeptide recognition sequence

32
Q

caspase 3 cleaves DFF45/ICAD and when it’s cleaved it releases

A

DFF40 which facilitates exposure of the nuclear localization signal on DFF40 allowing it to translocate to the nucleus

33
Q

IAPs

A

inhibitor of apoptosis - a family of cytoplasmic proteins

3 main ones: cIAP1, cIAP2, XIAP - they all bind to caspases 3,7,9

34
Q

XIAP is a potent

A

inhibitor of caspase activity

35
Q

SMAC/DIABLO

A

pro-apoptotic

found in mitochondrial membrane space and is released into the cytosol by conditions causing cytochrome c release

36
Q

FLIPS

A

inhibitor of apoptosis

really good inhibitor of death receptor apoptosis

37
Q

p35

A

a protein produced by a strain of baculovirus that is very potent inhibitor of virtually all caspases, has no effects on any other cysteine protease, forms irreversible covalent complex with caspases

38
Q

CrmA

A

a serpine protease inhibtor produced by cow pox virus
excellent inhibitor of caspases 1,8, 9
forms an irreversible complex with caspases

39
Q

role of caspases in non-apoptotic processes

A

DNA repair/cell cycle control (caspase2)
differentiation (caspase3, caspase14)
proliferation (caspase 8)

40
Q

Bcl-2 supergene family role in apoptosis

A

Bcl-2 could suppress the induction of mitochondrial apoptosis caused by multiple agents

41
Q

Bcl-2 anti-apoptotic members contain BH

A

1,2,3 and 4 domains

42
Q

two pro-apoptotic sub families

A

1 family contains BH 1,2,3 domains

other family contains BH 3 only domains

43
Q

Bcl-2 significance of binding partners

A

many of the Bcl-2 supergene family members can heterodimerize with another family member. this binding reflects the ability of the BH3 domain to bind to a hydrophobic cleft structure composed of BH1,2, and 3 domains

44
Q

significance of binding for Bcl-2 supergene family

A
  1. association of an anti-apoptotic member with a multi-domain pro-apoptotic member neutralizes the PRO-apoptotic member
  2. association of an anti-apoptotic member with BH3 domain only pro-apoptotic member neutralizes the ANTI-apoptotic
    member
  3. association of some BH3 domain only members with Bax or Bak results in Bax or Bak activation
45
Q

Bax and Bak have been shown to form pores in mitochondria - significance of pores

A
  1. facilitate the release of pro-apoptotic molecules like AIF, SMAC and cytochrome c from the mitochondria
  2. facilitate the release of lysosomal proteases from lysosomes. can cause apoptosis
46
Q

Bax and Bak are partially redundant in their functions

A

they are also the principal mediators of the intrinsic apoptotic pathway

47
Q

activation of cytoplasmic Bax is achieved by its complexing with

A

“activating BH3 proteins” like PUMA or Bim