6. Cell Cycle, Apoptosis, and Cancer

Question 1

What happens in the S phase?

Answer 1

DNA Replication

Histone Synthesis

Centrosome is formed

Chomosome is duplicated

Question 2

What happens in the M phase?

Answer 2

Mitosis

(Chromosome duplication and segregation, cytokenesis)

Question 3

What happens in G1?

Answer 3

RNA and protien synthesis preparing for DNA replication

Restriction point! If there aren’t enough growth factors or if there is DNA damage the cell doesn’t waste the energy to go into S phase.

Question 4

What happens in G2?

Answer 4

Peparation for Mitosis

DNA stability is checked and we make sure the entire genome was duplicated

Question 5

Where are the major regulatory points in the cell cycle?

Answer 5

G1: Growth factor restriction point and DNA damage checkpoint

G2: Checkpoint for complete DNA synthesis

Metaphase: Assures chromosomes are aligned and properly attached to microtubules (ideally)

Question 6

What complex is in charge of regulating the G1 regulatory step?

What molecules drive this reaction forward?

Answer 6

Rb/E2F

Myc activates G1-CDK, which phosphorylates Rb, causing it to let go of E2F

Question 7

What further phosphorylates Rb, even after G1-CDK?

What two molecules activate that kinase?

Answer 7

S-CDK

Cyclin E and Cyclin A

Question 8

Easy card:

What do CDK’s need to function?

Answer 8

Cyclin!

Question 9

What molecule can inhibit CDK+Cyclin after it’s been phosphorylated with CAK?

What molecule can re-activate it?

Answer 9

WEE-1

Hold my beer and watch this - WHEE. Explosion, fire, everything is broken (inactivated).

CDC25 phosphatase

Question 10

What does p27 do to the whole CDK-Cyclin complex?

Answer 10

Inhibits it by hugging it and preventing interaction with the active site.

Question 11

What drives the cell from Metaphase to Anaphase?

What enzyme does this?

How does it do this?

Answer 11

Destruction of obsolete cyclins; Cyclin S and Cyclin M

APC (Anaphase Promoting Complex)

It ubiquitinates the cyclin, targeting it for destruction by a proteosome.

Question 12

What is MDM2?

Answer 12

An E3 ubiquitin ligase

(He repeated this twice in the lecture, so I would know this)

Question 13

1. What allows p53 to act?
2. How does it do this?
3. What keeps p53 from acting normally?
4. What does p53 do?

Answer 13

1. DNA damage
2. leads to increased Protien Kinase activity, which phosphorylates p53, protecting it from ubiquitination.
3. MDM2 (That E3 ubiquitin ligase)
4. Activates p21, which turns off CDK, and keeps Rb hypophosphorylated (turned on), which sequesters E2F. Basically it stops the cell from moving forward.

Question 14

What do Caspases 3 6 and 7 have in common?

Answer 14

They are the bridge between Intrinsic and Extrinsic apoptosis pathways

Question 15

What are the two extrinsic death receptors?

Answer 15

FADD (FAS)

TRADD (TNF alpha)

Question 16

What do BAX and BAK do in apoptosis?

How do they do this?

Answer 16

They promote apoptosis.

Don’t worry, apoptosis. We’ve got your BAK or BAX

They stimulate the release of Cytochrome C (BAX opens a pore in the mitochondria)

Question 17

What do the BCLs do in terms of apoptosis?

How do they do this?

Answer 17

They inhibit apoptosis!

They inhibit the release of Cytochrome C

Question 18

What incites APAF-1 into its active form?

What is this active form called?

What can inhibit this change?

Answer 18

Cytochrome C

Apoptosome (Wheel of Death)

BCL-2

Question 19

Which apoptotic enzyme is activated by Cytochrome C / Apaf-1?

Answer 19

Caspase 9

Question 20

What is the name for genes that can become oncogenes?

What do these genes produce in normal cells?

Answer 20

Proto-Oncogenes

• Growth Factors
• Growth Factor receptors
• Transcription Factors
• Signal Transducers

Question 21

The overexpression of what EGF receptor is seen in many breast cancers?

What is the mutated form called?

Answer 21

HER2

NEU (A tyrosine Kinase that is always turned on, driving the cell cycle forward)

Question 22

Explain the “two hit hypothesis” relating to Rb.

Answer 22

Mutation of one copy of Rb1 in a heterozygous individual isn’t enough; but if a somatic mutation occurs as well (the second hit), then you have cancer.

Question 23

Why is sporadic Retinoblastoma so rare?

Answer 23

Because we have 2 normal Rb genes, and both have to mutate to cause the disease.

Question 24

What gene is associated with Chronic Myelogenous Leukemia?

What causes this gene to appear?

Answer 24

The BCR-ABL fusion gene.

Translocation of Chromosome 9 (carrying the ABL gene) to chromosome 22 (carrying the BCR gene).

Question 25

What disease is associated with an always-active EGF receptor due to a deletion in that receptor?

Answer 25

Glioblastoma

Question 26

What are ten “hallmarks of cancer cells” per Hanahan and Weinberg?

Answer 26

1. No need for external growth cell signals
2. Evasion of growth supressors
3. Invasion and metastasis
4. Replicative immortality (loss of telomeres)
5. Inducible angiogenesis
6. Resisting cell death (apoptosis)
7. Upregulating glycolysis
8. Avoiding T and B cells
9. Causing inflamation
10. High rate of mutation

Question 27

How do viral oncogenes work?

Answer 27

Viral genome integrates into a host genome, next to a proto-oncogene. The entire genome (including the proto-oncogene) is replicated like crazy. This counts as a “gain of function” mutation, and cancer can proliferate.

Question 28

What do Alkylating agents do?

Answer 28

Block DNA replication. (Chemotherapy)

Question 29

What drug is specifically targeted against HER2 mutations?

Answer 29

Trastuzumab

(Herceptin)

Question 30

What is Gleevec used for?

How does it work?

Answer 30

Threating Chronic Myelogenous Leukemia

Blocks a phosphorylation site on BCR ABL to prevent people with the BCR ABL gene from getting Chronic Myelogenous Leukemia.

Note: Creamer’s father had / has BCR ABL or CML, so I would know this one.