Cell Cycle, Apoptosis, and Cancer

Question 1

Stage of cell cycle were chromosome
duplication/segregation (start of cycle) and cytokinesis begins (end)

Answer 1

M Phase (M=Mitotic)

Question 2

Phases of Interphase

Answer 2

G₁, S, G₂

Question 3

Stage of cell cycle outside of normal dvision

Answer 3

G₀ Phase

Question 4

What phase does the RNA and protein synthesis needed for DNA replication occur.

Answer 4

Gap 1 phase of Interphase

Question 5

Phase of cell cycle where DNA stability is analyzed

Answer 5

Gap 2 (G₂) phase of Interphase

Question 6

Stage which ensures division is all set to happen (mitochondria are lined up, attached to the mitotic spindle, etc.)

Answer 6

M₁ (Mitosis)

Question 7

Descrete timepoint that exists if limiting growth factors occur.

At what time does this happen as well?

Answer 7

Restriction point

2hrs before S phase

Question 8

Prior to going into the S phase, this checkpoint occurs if there is DNA damage.

Answer 8

G₁ checkpoint (occurs end of G₁)

Question 9

Checkpiont that occurs if DNA replication did not occur ideally.

Answer 9

G₂ checkpoint (occurs end of G₂)

Question 10

How do mitogens induce moving from G₁ into the S phase?

Answer 10

Down stream in pathway Rb becomes phosphoralated

Rb normally sequesters E2F.

When phosphoralated it allows E2F to bind to DNA and allows the cell cycle to continue.

Question 11

How does Rb regulate itself and drive passed the G₁ checkpoint?

Answer 11

It promotes Cylin A and Cyclin E synthesis which further phosphoralate Rb and allow the cycle to continue.

Question 12

What are cyclins?

Answer 12

Cyclins bind to Cyclin Dependent Kinase to allow them to be active. They rise and fall dependent on stage of cell cycle.

DOES NOT FULLY ACTIVATE

Division increases them

Question 13

What in addition to cyclins do you need to activate Cyclin dependent kinases?

Answer 13

Cyclin-activating kinases (CAK)

Question 14

What are two examples of CDK1 inhibitors?

Answer 14

p27^Kip1 or WEE1

Question 15

How is the T-loop of CDK1 influinced by cyclin and CAK.

Answer 15

The t-loop blocks the active site.

Cyclin binds and allows it to move partially.

CAK binds in addition and moves it completely.

Question 16

What are the three main ways to regulate CDK1 activity?

Answer 16

Phosphorylation of CDK

Binding of CKI (p27 or WEE1)

Proteolysis with proteasomes

Question 17

Where does CAK phosphorylate CDK1

Answer 17

On the “cave site”

Question 18

How does WEE1 inhibit CDK1

Answer 18

Through phosphorylateing the “roof site”

Question 19

What does cdc25 do to CDK1?

Answer 19

Dephosphorylates the roof site (if phosphralated by inhibitory enzyme) to activate it.

Question 20

Does p27 phosphoralate CDK1?

Answer 20

No, it binds to CDK1 and cyclin complex preventing them from being active.

Question 21

When in cell cycle events does p27 inhibit CDK1?

Answer 21

Early events.

(G1 to S)

Question 22

How is mitotic division signaled to anaphase?

What is the key ubiquitin ligase invloved?

Answer 22

Cyclin turnover, it is ubiquitinated by anaphase promoting complex (APC/C) also know as cyclosome

Question 23

What cyclins are targeted by APC/C

Answer 23

S and M cyclins (A and B)

Question 24

What does normal p53 do?

What is it requlated by?

Answer 24

Signals for apotosis.

In healthy normal cells it is ubiquinated by MDM2

Question 25

What molecule does p53 increase in transcription rate? What does this do?

Answer 25

p21 p21 binds and inactivates CDK1 causing cell cycle arrest.

Question 26

Type of cell death where ligand binds to receptor.

Answer 26

Extrinsic

Question 27

What ligands are used in Extrinsic cell death?

Answer 27

Fas and TNF alpha

Question 28

Type of cell death originating from the mitochondria.

Answer 28

Intrinsic

Question 29

How are caspases activate?

Answer 29

Protease cleavage at certain sites to form a heterodimer with large and small subunits.

Question 30

What are example(s) of intiator caspases? What are example(s) of executioner caspases?

Answer 30

**Caspase 8 & 9** **Caspase 3,6,7**

Question 31

What is a major family of regulatory proteins in apoptosis?

Answer 31

The BCL2 family

Question 32

How does BAX (Bcl family) regulate apoptosis

Answer 32

In its inactive form it exists on the mitochondirial membrane. Upon activation **it aggregates to form a channel** that allows **cytc to spill out into the cytosol** and assist in **apoptosis.**

Question 33

What spills out from the mitochondria during cell death in addition to cytc?

Answer 33

Ca2+

Question 34

How is the Apotosome formed?

Answer 34

Through binding of **Cytc with Apaf1**

Question 35

What does the apotosome (Cytc/Apaf1 complex) activate?

Answer 35

Caspase-9

Question 36

What constitutes a Proto-oncogene?

Answer 36

Things that regulate cell growth and division: Growth factors GF receptors and hormones Transcription factors Signal transducers

Question 37

How are oncogenes formed?

Answer 37

Gain of function mutations in proto-oncogenes Too much product Alternative product (oncoproteins)

Question 38

What is a mutation happens to proto-oncogene HER2 and what kind of Cancer is it commonly found in?

Answer 38

**HER2** has a tyrosine kinase domain and is active upon binding a ligand. It becomes **NEU** upon mutation and is **activated without a ligand.** **Breast cancer**

Question 39

What does EGF receptor become as an oncogene? What disease does this become?

Answer 39

**EGFRvIII** (tyrosine constitutively active) ## Footnote **Glioblastoma**

Question 40

What does BCR fuse with as a gain of function mutation due to translocation? What disease is this related to?

Answer 40

**ABL** **Chronic Mylogenous Leukemia**

Question 41

How is Retinoblasoma formed?

Answer 41

One mutation exists in the RB₁ gene on one allele. Second allele is hit resulting in the disease as RB₁ no longer exists. (**Tumors in both eyes may form**)

Question 42

Sporadic Retinoblastoma

Answer 42

Mutation in 2 RB genes Super Rare

Question 43

What are the functions of Tumor Supressor genes?

Answer 43

Repress cell cycle progression Promote apoptosis Couple DNA damage with the cell cycle

Question 44

BRCA is associated with what cancer?

Answer 44

Its a **tumor supressor** associated with **breast cancer**

Question 45

TP53 or p53 is associated with what cancers?

Answer 45

a. 65% of colon cancers b. 30-50% of breast cancers c. 50% of lung cancers

Question 46

PTEN- Phosphatase and tensin homolog is associated with what cancer?

Answer 46

%70 of **p**rostate cancers **P**TEM

Question 47

APC- Adenomatous polyposis coli is associated with what cancers?

Answer 47

Colon cancer

Question 48

What are the functions of Metastasis Suppressor proteins?

Answer 48

Prevent tumor cells from despersing Block loss of contact inhibition Inibit tumor metastasis

Question 49

Describe the development of cancer and the "multi hit hypothesis"

Answer 49

1. Mutation occurs in cell 2. This cell proliferates. 3. Multiple mutations in tumor supressor genes 4. Mutations in metastisis inhibitory proteins / other modifications 5. Metastisis

Question 50

10 fundamental things of cancer

Answer 50

1. Growth Signals 2. Evade growth supressors 3. Metastasis 4. Immortality (through replication) 5. Angiogenisis 6. Resist Death **7. Disregulate cell energetics** 8. Aviod Immune 9. Inflammation 10. Genome instability

Question 51

How can HPV cause cancer?

Answer 51

Can cause degredation of **p53 through E6** Can cause sequesteration of **RB through E7**

Question 52

Agents that block or supress DNA replication.

Answer 52

Alkalating Agents - everything Anti-metabolites - S phase Topoisomerase I Inhibitors - S phase Topoisomerase II Inhibitors - S phase, G2 phase, and M Citotoxic antibodies - S phase and G2 phase Mitotoxic inhibitors - M phase

Question 53

Drug used to block HER2 and Neu? How does it work?

Answer 53

Herceptin Acts as an antibody that blocks cleavage, dimerization, activates antibody dependent cytotoxisity, causes endocytosis.

Question 54

Drug used to block BCR-ABL protein?

Answer 54

Gleevic Competitively binds to where the ATP binds

Question 55

What drug inhibits EGF?

Answer 55

Erbitux

Question 56

G₁ phase CDK and Cyclins

Answer 56

Cylcin D CDK4 CDK5

Question 57

CDK and Cyclin for G₁/S phase

Answer 57

Cyclin E CDK2 (**Inhibited by CKI**)

Question 58

Cyclin and CDK for S phase

Answer 58

Cyclin A CDK2 Inhibited by CKI

Question 59

Cyclin and CDK for M Phase

Answer 59

Cyclin A and Cyclin B CDK1