Cell Cycle, Apoptosis and Cancer

Question 1

What are the stages of the cell cycle?

Answer 1

Mitosis- nuclear division
Interphase- G1, S and G2
G0 phase- withdraw from cell cycle

Question 2

What is G1 phase>

Answer 2

Gap 1 phase- RNA and protein synthesis needed for DNA replication

Question 3

What is the S phase?

Answer 3

Phase of DNA synthesis

Question 4

What is G2 phase?

Answer 4

Gap 2 phase- DNA stability is checked

Question 5

Restriction point

Answer 5

Occurs in G1- Cell must receive growth factors to move past restriction point. Occurs about 2 hours prior to S phase.

Question 6

G1 checkpoint

Answer 6

occurs around the same time of restriction point- Occurs in response to DNA damage before replication

Question 7

G2 checkpoint

Answer 7

Verify the completion of genomic duplication

Question 8

Metaphase checkpoint

Answer 8

Ensures that the chromosomes are attached to mitotic spindles for proper separation

Question 9

Cell proliferation

Answer 9

Myc-TF will increase gene expression of G1 cyclin dependent kinase- CDK then phosphorylates retinoblastoma, releasing the E2F protein.

Question 10

What is the factor that drives G1 to S phase?

Answer 10

The release of E2F from phosphorylated Rb will begin s phase gene transcription

Question 11

What genes do E2F stimulate?

Answer 11

Transcription of Cyclin E and Cyclin A which activates CDK2

Question 12

Feedback of cell proliferation

Answer 12

Cyclin E-CDK2 and Cyclin A-CDK2 keep Rb in hyperphosphorylated state. Transcription of genes also create a positive feedback loop

Question 13

Activation of cyclin-CDK activity

Answer 13

Cyclin binds to CDK which partial activates the t loop but full activation requires CDK-activating Kinase to phorphorylate the t-loop

Question 14

What cyclin-CDK complexes get past restriction point?

Answer 14

Cyclin D- CDK4 and Cyclin D-CDK6

Question 15

Inhibition of cyclin-CDK activity

Answer 15

Wee1 kinase inhibits by phosphorylating “roof site” of complex
p27 will bind to both cyclin and CDK to inactivate the complex

Question 16

What is the function of cdc25 phosphatase?

Answer 16

It will dephosphorylate roof site after Wee1 inactivates CDK complex

Question 17

What is APC/C?

Answer 17

Anaphase-promoting complex- a member of the ubiquitin ligase family. it regulates the progression from metaphase to anaphase.

Question 18

What is ubiquitin?

Answer 18

a small protein that is attached to the lysine residues of proteins to signal destruction of the protein

Question 19

How does the cell cycle move into anaphase?

Answer 19

CDC20 will activate APC/C leads to the addition of polyubiquitin to S and M cyclins. The destruction of cyclins inactivates the CDK and allows for progression into anaphase.

Question 20

what is p53?

Answer 20

The guardian of the genome- responds to DNA damage and will regulate transcription to halt cell cycle

Question 21

What is the process for activation of p53?

Answer 21

DNA damage will activate protein kinase. p53 will then be phosphorylated and begin transcription of genes for p21

Question 22

What is p21?

Answer 22

It is a cyclin-dependent kinase inhibitor (CKI) and will primarily inhibit CDK2

Question 23

What is the intrinsic pathway of apoptosis?

Answer 23

Mitochondrial dependent- responds to DNA damage, lack of O2, nutrients or extracellular survival signals

Question 24

What is the extrinsic pathway of apoptosis?

Answer 24

It is a mitochondrial independent cycle

Question 25

Capase activation

Answer 25

Capase are responsible for apoptosis. Activated by protease cleavage. Will make a heterodimer that forms from a small and a large subunit

Question 26

What are the two initiator proteins of apoptosis?

Answer 26

Capase 8 and capase 9

Question 27

What are the executioner proteins of apoptosis?

Answer 27

Destroys the targets and executes apoptosis. Ex is Capase 3, 6 and 7- They are activated by capase 8 and 9

Question 28

Describe the intrinsic pathway of apoptosis

Answer 28

Capase 8 is activated which will then stimulate BAX. BAX then aggregates in the mitochondrial membrane, releasing cytochrome C into the cytosol. Cyto C and hydrolysis of ATP activates Apaf1 creating an apoptosome. This then recruits and activates procapase 9 leading to the activation of executioner proteins.

Question 29

What is a proto-oncogene?

Answer 29

Growth factors, receptors of GFs, transcription factors and signal transducers- Most are involved in cell growth and division

Question 30

What is an oncogene?

Answer 30

a mutation in a proto-oncogene that results in increased expression of proteins and causes the cell to act abnormally. Most result in cancer mutations

Question 31

What is the HER2 gene?

Answer 31

Tyrosine Kinase Receptor. Mutation causes overexpression of HER2, seen in many breast cancers

Question 32

Tumor suppressor examples

Answer 32

RB1- causes retinoblastomas TP53 PTEN- phosphatase and tensin homolog- prostate cancer APC- Adenomatous polyposis coli- Colon cancer

Question 33

What is Herceptin?

Answer 33

An inhibitor of oncoproteins- HER2

Question 34

What is Gleevec?

Answer 34

An inhibitor of oncoproteins- BCR-ABL

Question 35

What is Erbitux?

Answer 35

An inhibitor of oncoproteins- EGF receptors