L5: Regulation of Cell Cycle & Apoptosis

Question 1

What regulates the cell cycle?Specify which one is direct and which one is indirect.

Answer 1

Regulated by 2 tumour suppressors:

• DIRECTLY by Rb (Retinoblastoma) protein
• INDIRECTLY by p53 tumour suppressor

Question 2

If a cells doesn’t enter into an active cell cycle what does it do?

Answer 2

enters G0 - quiescent state

Question 3

what would prevent a cell from entering the mitosis phase of the cell cycle?

Answer 3

if DNA replication is not completed in G2

Question 4

what would prevent a cell from entering the anaphase stage of mitosis?

Answer 4

blocked if chromatids are not properly assembled on the mitotic spindle

Question 5

where is the DNA damage check point? what happens if genome damage is detected?

Answer 5

R point in G1

if genome damage is detected entrance into S phase is blocked

Question 6

in the S phase of the cell cycle, what happens if the genome is damaged

Answer 6

DNA replication is halted

Question 7

Which are the cell cycle proteins?

Answer 7

cyclins, CDKS and CKI

Question 8

What are cyclins?

Answer 8

proteins that are expressed in a specific manner during the cell cycle. They form a complex with cyclin dependent kinases, CDKs, and ACTIVATE them.

Question 9

What are CDK?

Answer 9

Cyclin Dependent Kinases, that phosphorylate specific substrates at serine/threonine residues.

Question 10

Which Cyclin Dependent Kinase Inhibitors are involved in the cell cycle

Answer 10

p21, p27 & p57 proteins

Question 11

which point in the cell cycle is usually deregulated cancer cells?

Answer 11

R/Restriction point

Question 12

After cells go through R point, what happens with the activated kinases?

Answer 12

After cells go through R-point
each activated kinase sequentially activates the next kinase and inhibits the previous kinase for the cell cycle to proceed smoothly without further regulation

Question 13

Name the different kinases active during each phase of the cell cycle and the cyclins that activyate them.

Answer 13

1. Mitosis:
CDK: CDC2 
Cylin B
2. G1:
CDK: CDK4/6
Cyclin D 
3.G1 After R point:
CDK: CDK2
Cylcin E
4 S:
CDK: CDK2
Cyclin A 
S phase to G2 phase 
CDK: CDC2 aka CDK1
Cyclin A

Question 14

During cell cycle progression the cyclin D-CDK4/6 complex becomes an active kinase that phosphorylates what?

Answer 14

Retinoblastoma (Rb) protein.

Question 15

During cell cycle progression hyper-phosphorylation of Rb protein is dependent on what?

Answer 15

cyclin E-CDK2

Question 16

During cell cycle progression hyper-phosphorylation of Rb protein allows what?

Answer 16

Hyper-phosphorylated Rb releases the E2F transcription factors to allow cells to go into S phase.

Question 17

what does p53 function as?

Answer 17

as a DNA-damage inducible, DNA sequence specific transcription factor.

Question 18

p53 co-ordinates what?

Answer 18

p53 co-ordinates the cellular response to genotoxic stress and has been called the ‘Guardian of the Genome’.

Question 19

what is the most commonly mutated tumour suppressor?

Answer 19

p53

Question 20

how does mutant p53 behave?

Answer 20

behaves as a dominant oncogene, which frequently spans the benign to malignanttransition step.

Question 21

which CKIs inhibits

D-CDK4/6

Answer 21

p16 INK4A
p15 INK4B
p18 INK4C
p19 INK4D

Question 22

which CKIs inhibit E-CDK2, A-CDK2, A-CDC2 and B-CDC2.

Answer 22

p57 Kip2
p27 Kip1
p21 Cip 1