Cell Cylce, Apoptosis, And Cancer

Question 1

What are the phases of the cell cycle?

Answer 1

G1–Gap phase one—RNA and protein synthesis needed from DNA replication.

S-phase—DNA is synthesized

G2–Gap 2 phase, DNA stability is checked.

G0–if poor nutrients/environment conditions—cell will withdraw from cycle. (This happens after G1 if needed)

M-phase—mitosis at the beginning, cytokinesis at the end.

Question 2

What are the check points/restriction points of the cell cycle?

Answer 2

Restriction point (R)—if growth factors are present, move through restriction and continue. If growth factors not present, don’t grow—move to G0

G1 check point—occurs in response to DNA damage. Fix the DNA before we replicate it.

G2 check point–genes have been duplicated, make sure its right.

Metaphase checkpoints—ensures that the chromosomes are attached to the mitotic spindle before division.

Question 3

Mutations in proteins that regulate the cell cycle lead to what?

Answer 3

Uncontrolled cell division and proliferation»»>CANCER

Question 4

What is a mitogen

Answer 4

A growth factor that induces mitosis

Question 5

What protein sequesters E2F, and how does E2F get release?

What is even E2F?

Answer 5

Retinoblastoma (Rb) holds on to EF2 until it is phosphorylated by CDK.

E2F is a transcription factor that drives the cell from G1 to S phase by upregulating the expression of Cyclin E and Cyclin A.

These cyclins are needed to activate CYCLIN DEPENDENT KINASES, y’all

Question 6

What gene regulatory protein drives cell proliferation?

What does he do?

Answer 6

Myc!

Increases G1-CDK levels.

Question 7

Besides Cyclin, what do you need to activate CDK?

Answer 7

You also need CAK, to phosphorylate that lil T-loop to get him out of the way. This fully activates the enzyme.

Question 8

What inhibits CDK?

Answer 8

p27–binds the entire active Cyclin-CDK complex

WEE 1—is a kinase and phosphorylates the fully active Cyclin-CDK a the “roof site” to make it inactive

Question 9

What is the function of G1 Cyclin D, and what complexes does it make?

Answer 9

It helps the passage of cells through the restriction point late in G1 phase.

Makes Cyclin D-CDK4, and Cyclin D-CDK6

Question 10

What is true about cyclins and CDKs as we progress through the cell cycle?

Answer 10

The expression and activity of the different types will rise and fall in conjunction with the different phases.

Question 11

How do we progress from metaphase to anaphase?

Answer 11

• triggered by cyclin turnover.
• key regulator here is anaphase-promoting complex (APC/C) also know as cyclosome.
• the cyclosome is a member of the ubiquitin ligase fam

Question 12

What kind of proteins does APC/C ubiquitinate, why?

Answer 12

• Ubiquitinates S- and M- cyclin proteins.
• cyclins are destroyed.
• if no cyclin, CDK doesn’t work, and its time for the next phase.

Question 13

What is p53 and why is it so important?

Answer 13

p53 is the “guardian of the genome”

A transcription factor that is phosphorylated to become active and increases the transcription of p21»which causes the cell cycle to stop if there is a problem.

Breakdown in this gene leads to cancer.

Question 14

What is p21 and why is it important?

Answer 14

• p21 is a CDK-inhibitor.
• It associates with CDK2.
• this association stops cyclin/CDK complexes and therefore arrests the cell cycle.

Question 15

What is apoptosis?

Answer 15

Programmed cell death.
The organized break-down of the cell.

Not like necrosis.

Question 16

What are the two pathways for apoptosis?

Answer 16

Extrinsic (death receptor) pathway

Intrinsic (mitochondrial) pathway

Question 17

Explain the extrinsic pathway

Answer 17

FAS ligands and TNF bind to FAS receptors and TNF receptors respectively.
These receptors are bound to FADD and TRADD respectively.
FADD and TRADD both activate procaspase-8 into caspase-8.
Caspase-8 activates caspases-3,-6,-7 which trigger apoptosis via cell surface alteration, cytoskeleton reorganization, and endonuclease activity.

Question 18

Describe the intrinsic pathway

Answer 18

• Apoptotic stimulus activate BAX to aggregate in the mitochondrial membrane.
• BAX creates pores in the membrane and allows cytochrome c to leave the mitochondria
• cytochrome c binds APAF-1 to form the apoptosome.
• apoptosome activates procaspase-9 to caspase-9.
• Caspase-9 activates caspasaes-3,-6,-7
• apoptosis

Question 19

Things that are PRO-APOPTOTIC

Answer 19

1. p53
2. BAX
3. BAK
4. FADD
5. TRADD
6. TBid

Question 20

Things that are ANTI-APOPTOTIC (Pro survival)

Answer 20

1. BCL-2

2. BCL-xl3

Question 21

What happens when HER2 receptor is mutated?

Answer 21

• Val changes to Glu on the ECD.
• receptor acts like the ligand is always bound
• signal is perpetually sent
• cells keep dividing

BREAST CANCER

Question 22

Sporadic form of retinoblastoma

Answer 22

Non hereditary
RARE
Cancerous cells have both copies of RB1 mutated.

Question 23

Examples of tumor suppressor genes

Answer 23

1. BR1 (encodes Rb)
2. TP53 (encodes p53)
3. PTEN (phosphatase and tension homolog)
4. APC (Adenomatous polyposis coli)

Question 24

What are the 10 hallmarks of cancer

Answer 24

1. Self-sufficiency in growth signals
2. Evading growth suppressors
3. Activation invasion and metastasis
4. Enabling replicative immortality
5. Inductively angiogenesis
6. Revisiting cell death
7. Deregulating cellular energetic
8. Tumor-promoting inflammation
9. Avoiding immune destruction
10. Genomes instability and mutation

Question 25

ALKYLATING AGENTS block what step of the cell cycle?

Answer 25

Block DNA replication

Question 26

TOPOISOMERASE I INHIBITORS block what step of the cell cycle?

Answer 26

Inhibit S phase by inhibiting Topoisomerase and causing tangles and supercoilng in DNA

Question 27

ANTIMETABOLITES block what step of the cell cycle?

Answer 27

The S-phase.

Inhibit enzymes that are involved in DNA synthesis

Question 28

CYTOTOXIC ANTIBIOTICS block what step of the cell cycle?

Answer 28

S-phase and G2

Intercalated between bases in DNA to inhibit DNA synthesis

Question 29

TOPOISOMERASE II INHIBITORS block what step of the cell cycle?

Answer 29

S-phase, G2 phase, and M phase

Cause DNA supercoiling during DNA synth

Question 30

MITOTIC INHIBITORS block what step of the cell cycle?

Answer 30

M-phase

Arrest cells in mitosis during metaphase.