19.3 Programmed Cell Death

Question 1

() balances cell proliferation and potentially dangerous cells (e.g. virus-infected cells, cells with damaged DNA/mutated DNA)

Answer 1

programmed cell death

Question 2

3 main events in apoptosis:

Answer 2

1. DNA fragmentation
2. chromatin condensation
3. fragmentation of nucleus

Question 3

membrane-enclosed fragments that result from the apoptosis of cells

Answer 3

apoptotic bodies

Question 4

how are cells that die by apoptosis rapidly removed from tissues

Answer 4

apoptotic bodies are efficiently recognized and phagocytosed by both macrophages and neighboring cells

Question 5

apoptopic cells express () on their surface

Answer 5

‘eat me’ signals (e.g. phosphatidylserine)

Question 6

apoptosis causes () to be expressed on the cell surface, where it is recognized by receptors expressed by phagocytic cells

Answer 6

phosphatidylserine

Question 7

studies of () by Horvits and colleagues identified 3 genes with key roles in apoptosis:

Answer 7

C. elegans

Question 8

studies of C. elegans by Horvits and colleagues identified 3 genes with key roles in apoptosis:

Answer 8

1. Ced-3
2. Ced-4
3. Ced-9

Question 9

(1) and (2) are genes that are required for developmental cell death

Answer 9

Ced-3 and Ced-4

Question 10

Ced-9 serves as a () in apoptosis

Answer 10

negative regulator

Question 11

Ced-3 was found to be the prototype of the ()

Answer 11

caspases (a family of proteases)

Question 12

() was found to be the prototype of the caspases (a family of proteases)

Answer 12

Ced-3

Question 13

called caspases due to the presence of (1) at their active sites and they cleave (2) in their substrate proteins

Answer 13

1. cysteine (C) residues
2. aspartic acid (Asp) residues

Question 14

the () are the ultimate effectors/executioners of programmed cell death; they bring about apoptosis by cleaving more than 100 different target proteins

Answer 14

caspases

Question 15

activation of an () starts a chain reaction of caspase activation leading to cell death

Answer 15

initiator caspase

Question 16

main targets of caspases in apoptosis

Answer 16

1. DNase inhibitor
2. nuclear lamins
3. cytoskeletal proteins
4. Golgi matrix proteins
5. scramblase

Question 17

caspases targeting DNase inhibitor results in DNase activation, which in turn results in ()

Answer 17

nuclear DNA fragementation

Question 18

caspases cleave nuclear lamins to result in ()

Answer 18

fragmentation of nucleus

Question 19

caspases cleave cytoskeletal proteins to result in ()

Answer 19

cytoskeletal disruption, cell fragmentation, and PM blebbing (irregular bulging)

Question 20

caspases cleave Golgi matrix proteins to result in ()

Answer 20

fragmentation of Golgi

Question 21

caspases also cleave and activate a () that translocates phosphatidylserine to the outer leaflet of the PM

Answer 21

scramblase

Question 22

higher eukaryotes have families of at least 7 caspases that are classified as either (1) or (2) caspases

Answer 22

1. initiator
2. effector

Question 23

all caspases are synthesized as inactive precursors called ()

Answer 23

procaspases

Question 24

procaspases are converted to the active form by () (catalyzed by other caspases)

Answer 24

proteolytic cleavage

Question 25

() caspases are activated in response to various signals

Answer 25

initiator

Question 26

() are cleaved and activated by initiator caspases and then act to digest cellular target proteins

Answer 26

effector caspases

Question 27

Ced-9 was found to be closely related to a mammalian gene called (), an oncogene that contributed to the development of B-cell lymphomas

Answer 27

bcl-2

Question 28

instead of stimulating cell proliferation, bcl-2 was found to ()

Answer 28

inhibit apoptosis

Question 29

2 major classifications of Bcl-2 family members

Answer 29

1. antiapoptotic regulatory proteins 2. proapoptotic proteins

Question 30

proapoptotic proteins can be further divided into

Answer 30

1. proapoptotic regulatory proteins 2. proapoptotic effector proteins

Question 31

act to induce caspase activation and promote cell death

Answer 31

proapoptotic proteins

Question 32

inhibit proapoptotic effector proteins (e.g. Bcl-2) and are regulated by signals that induce cell death or survival

Answer 32

proapoptotic regulatory proteins

Question 33

downstream effectors that directly induce apoptosis

Answer 33

proapoptotic effector proteins

Question 34

activated proapoptotic regulatory proteins initiate apoptosis by 2 mechanisms:

Answer 34

1. antagonize antiapoptotic regulatory proteins 2. activate proapoptotic effector proteins

Question 35

in mammals, Bcl-2 family proteins act at the ()

Answer 35

mitochondria

Question 36

proapoptotic effector proteins (1) oligomerize to form pores in the outer mitochondrial membrane to release (2)

Answer 36

1. Bax and Bak 2. cytochrome c

Question 37

release of () triggers caspase activation

Answer 37

cytochrome c

Question 38

key initiator caspase in mammalian cells

Answer 38

caspase-9

Question 39

caspase-9 is activated by forming a complex with (1) in a multisubunit complex called (2)

Answer 39

1. Apaf-1 2. apoptosome

Question 40

pathways that regulate programmed cell death are either:

Answer 40

1. intrinsic pathways 2. extrinsic pathways

Question 41

programmed cell death regulatory pathways that are triggered by DNA damage and other cell stress

Answer 41

intrinsic pathways

Question 42

intrinsic pathways are triggered by (1) and other (2)

Answer 42

1. DNA damage 2. cell stresses

Question 43

the multiple signals that activate intrinsic apoptosis regulatory pathways converge on regulation of ()

Answer 43

proapoptotic regulatory Bcl-2 proteins

Question 44

programmed cell death regulatory pathways that are triggered by signals from other cells

Answer 44

extrinsic pathways

Question 45

extrinsic apoptosis regulatory pathways are activated by ()

Answer 45

signals from other cells

Question 46

give examples of intrinsic pathways that regulate apoptosis

Answer 46

1. p53 pathway 2. Akt/PI 3-kinase pathway

Question 47

transcription factor p53 mediates a major pathway that leads to cell cycle arrest in response to ()

Answer 47

DNA damage

Question 48

the Akt/PI 3-kinase pathway is an intrinsic pathway that regulates apoptosis; it responds to ()

Answer 48

growth factor deprivation

Question 49

(1) and (2) protein kinases (activated by DNA damage) phosphorylate and stabilize p53

Answer 49

1. ATM 2. Chk2

Question 50

induction of apoptosis due to increased p53 is due in part to the transcriptional activation of genes encoding () (proapoptotic regularory proteins)

Answer 50

PUMA and Noxa

Question 51

increased PUMA and Noxa lead to activation of ()

Answer 51

Bax and Bak

Question 52

most cells in higher animals are programmed to undergo apoptosis unless cell death is ()

Answer 52

actively supressed by survival signals from other cells (e.g. growth factors)

Question 53

a major pathway that promotes cell survival is initiated by (1) and results in the activation of (2)

Answer 53

1. PI 3-kinase 2. Akt

Question 54

how does Akt regulate proteins involved in apoptosis

Answer 54

Akt phosphorylates BH-3 proteins including Bad and FOXO transcription factors to inactivate them

Question 55

in absence of Akt, (1) promotes apoptosis and (2) stimulates transcription of another proapoptotic BH3-only protein called (3)

Answer 55

1. Bad 2. FOXO 3. Bim

Question 56

example of extrinsic pathway that regulates programmed cell death

Answer 56

TNF-receptor signaling

Question 57

polypeptides in the () family bind to receptors and activate an initiator caspase

Answer 57

tumor necrosis factor

Question 58

polypeptides in the tumor necrosis factor family bind to receptors and activate an initiator caspase called ()

Answer 58

caspase-8

Question 59

caspase-8 cleaves and activates (1) and (2), which leads to the activation of (3)

Answer 59

1. effector caspases 2. Bid 3. caspase-9

Question 60

() - provides a mechanism for the gradual turnover of the cell’s components through lysosomes

Answer 60

autophagy

Question 61

autophagy can lead to cell death by ()

Answer 61

degradation of essential cell components

Question 62

accidental cell death from acute injury; causes swelling and bursting of the cell

Answer 62

necrosis

Question 63

unlike apoptosis, autophagy does not require ()

Answer 63

caspases

Question 64

in necrosis, cell contents are released into extracellular space and cause ()

Answer 64

inflammation

Question 65

regulated necrotic cell death

Answer 65

necroptosis