04a: Cell Cycle and Apoptosis

Question 1

Give examples of adult cells that don’t undergo proliferation.

Answer 1

Nerve, striated muscle, cardiomyocytes

Question 2

Give examples of adult cells that undergo frequent proliferation.

Answer 2

Fibroblasts, Bone marrow, Myeloid

Question 3

A non-dividing cell is in (X) phase.

Answer 3

X = Go

Question 4

Following the appropriate stimulus, cell enters cycle of division and proceeds through which phases (in order).

Answer 4

1. G1
2. S
3. G2
4. Mitosis

Question 5

Cell undergoes (X) in G1.

Answer 5

X = Growth and metabolism

Question 6

Cell undergoes (X) in S.

Answer 6

X = DNA replication

Question 7

Cell undergoes (X) in G2.

Answer 7

X = Preparation for division

Question 8

Chromosome number in G1.

Answer 8

2n (diploid)

Question 9

Chromosome number in S.

Answer 9

2n to 4n

Question 10

Chromosome number in G2.

Answer 10

4n

Question 11

Chromosome number in M.

Answer 11

4n to 2n

Question 12

Condensing chromosomes indicate (interphase/prophase).

Answer 12

Prophase

Question 13

Anaphase in mitosis involves separation of:

Answer 13

two sister chromatids

Question 14

Give examples of cells that skip certain cell cycle phases. Which phase(s) does each skip?

Answer 14

1. Megakaryocyte (late anaphase and cytokinesis)

2. Trophoblast (late anaphase and cytokinesis)

Question 15

(X) cells have abnormal, uneven segregation of chromosomes, resulting in (haploid, polyploid, uneuploid) cells.

Answer 15

X = cancer

Uneuploid

Question 16

Disease associated with (X) cause reduction in reduced platelet counts?

Answer 16

X = decreased polyploidy in megakaryocytes

Question 17

Cyclin D peaks primarily in which phase?

Answer 17

G1

Question 18

Cyclin E peaks primarily in which phase?

Answer 18

S

Question 19

Cyclin A peaks primarily in which phase?

Answer 19

S (and a bit into G2)

Question 20

Cyclin B peaks primarily in which phase?

Answer 20

Late G2, and into M

Question 21

Which proteins are important for entrance/transitions into/out of cell cycle phases?

Answer 21

Cyclins

Question 22

Cyclin forms an active complex when coupled with:

Answer 22

CDK (cyclin-dependent kinase)

Question 23

What are CKIs? List examples.

Answer 23

CDK inhibitors

p16, p21, p27

Question 24

CKIs inhibit which specific reaction?

Answer 24

Phosphorylation by active Cyclin-CDK complex

Question 25

High levels p16 effect on cell cycle.

Answer 25

Inhibits Cyclin D (coupled with CDK 4 or 6); so stops cell from entering G1 phase

Question 26

High levels of p21 effect on cell cycle.

Answer 26

Inhibits Cyclin E (coupled with CDK 2); halts cycle

Question 27

High levels of p27 effect on cell cycle.

Answer 27

Inhibits Cyclin E or A (coupled with CDK 2); halts cycle

Question 28

Whats the function of the CDC2-Cyclin B complex?

Answer 28

Activates proteins on the chromosomes that are responsible for chromosome segregation.

Question 29

What's the primary control mechanism for CKIs?

Answer 29

Transcription regulation

Question 30

Rb is known as a(n):

Answer 30

Tumor suppressor

Question 31

Free E2F function:

Answer 31

Activates genes that regulate DNA synthesis

Question 32

E2F, bound to (X), function:

Answer 32

X = Rb Function (activates genes for DNA synthesis) is suppressed

Question 33

CDK-cyclins affect (Rb/E2F) in which way(s)?

Answer 33

Affect both! Directly phosphorylate Rb, so can't bind E2F. This allows E2F to carry out function of gene activation (cell cycle proceeds)

Question 34

CKI affect (Rb/E2F) in which way(s)?

Answer 34

Indirectly allow cell cycle arrest by inhibiting Cyclin-CDK complex from phosphorylating Rb.

Question 35

Necrotic cell death involves (X) and occurs as result of (Y).

Answer 35

X = lysis of membrane and release of cell content Y = trauma or infection

Question 36

Apoptosis is result of (X) activation by (Y) signals.

Answer 36

``` X = caspases Y = intracellular biochemical signals ```

Question 37

Caspases are specifically (X) enzymes, so they act to:

Answer 37

X = cysteine protease Hydrolyze specific peptide bonds

Question 38

Caspases are initially produced as:

Answer 38

Inactive pro-caspases

Question 39

What initial step allows activation of the caspase cascade?

Answer 39

Pro-caspases (8, 9, 10) are autocatalytic, so cleave themselves to produce active caspases

Question 40

Active caspases 8-10 act on:

Answer 40

Caspases 3, 6, 7 (cleave them)

Question 41

Active Caspases 3, 6, 7 act on:

Answer 41

Other cellular proteins

Question 42

An apoptotic cell undergoes changes in which structure(s)?

Answer 42

1. Plasma membrane 2. Cytoskeleton 3. Nuclear DNA (fragmentation)

Question 43

In apoptotic cell, degradation of chromosomal DNA is carried out by:

Answer 43

Endonucleases (caspase-activated DNase)

Question 44

Fate of remains of apoptotic cell

Answer 44

Uptaken and digested by macrophages

Question 45

What are the main pathways to apoptosis?

Answer 45

1. Death receptor pathway | 2. Mitochondrial pathway

Question 46

Whats TNF-a?

Answer 46

Death ligand that, upon binding death receptor, initiates apoptosis via death receptor path

Question 47

List steps that initiate death receptor pathway.

Answer 47

1. TNF-a binds Fas death receptor 2. Intracellular adaptor protein (FADD) binds to cytoplasmic side of death receptor 3. Recruits pro-caspase (8-10), which undergo autocatalytic activity and initiate caspase cascade

Question 48

Under normal conditions, cytochrome C is present in/on:

Answer 48

In mitochondrial intermembrane space

Question 49

Under apoptotic conditions, cytochrome C is present in/on:

Answer 49

Translocated to cytosol via pores

Question 50

Upon leaving mitochondria, cytochrome c:

Answer 50

Binds Apaf1 and pro-caspase 9, forming apoptosome

Question 51

What's the apoptosome?

Answer 51

Complex of: 1. Cytochrome c 2. Apaf1 3. Pro-caspase 9

Question 52

What regulates Cytochrome C release from mitochondrion?

Answer 52

Channels (Bcl proteins)

Question 53

Bcl proteins are divided into (X). List examples of each.

Answer 53

X = 1. Anti-apoptotic: Bcl-2 and Bcl XL 2. Pro-apoptotic: Bax and Bak

Question 54

Bcl-2 activity has what effect on Cytochrome C movement?

Answer 54

Prevent formation of membrane pores through which Cytochrome C would leave mitochondria

Question 55

The mitochondrial membrane pores are composed of:

Answer 55

Dimers or polymers of Bax and Bak

Question 56

List some facilitators of Bax and Bak. What effect do these have on apoptosis?

Answer 56

Bid, Bad, Noxa Promote apoptosis

Question 57

T/F: the presence of Bax/Bak facilitators determines cell death or survival.

Answer 57

False - ratio between anti- and pro- apoptotic proteins is determinant of cell death/survival

Question 58

XIAP is (X) with affinity for (Y).

Answer 58

X = caspase inhibitor protein Y = active caspases

Question 59

What's the Smac-DIABLO pathway?

Answer 59

Apoptotic pathway in which Smac/DIABLO protein inhibits apoptotic/caspase inhibitor XIAP

Question 60

The p53 protein is an example of a(n) (X) that acts by affecting:

Answer 60

X = tumor suppressor Transcription (regulates expression of various genes)

Question 61

How does p53 (prevent/induce) apoptosis?

Answer 61

Induces 1. Increases transcription of Bax and Noxa 2. Activates cytoplasmic Bax to bind mitochondrial membrane 3. Increases p21 expression (cell cycle arrest)

Question 62

Raf, a(n) (X) protein, (prevents/induces) apoptosis by:

Answer 62

X = MAP kinase Prevents; Phosphorylates Bad, leading it to dissociate from mitochondrial membrane

Question 63

One way to prevent apoptosis is (X) of Bad, causing its (increased/decreased) enhancing action on (Y). Name some enzymes that have this function.

Answer 63

X = Phosphorylation Decreased Y = Bax and Bcl-XL Raf and Akt