Cell Proliferation II

Question 1

Transcription Factor (3)

Answer 1

• proteins which control gene expression
• activated by proliferative signal
• encode genes that result in synthesis of proteins required to activate and control cell division

Question 2

Name 3 cell cycle regulators (3)

Answer 2

• cyclins
• cyclin dependent kinases (Cdk)
• Cdk inhibitors (CKI)

Question 3

What do cyclin-Cdk complexes possess?

Answer 3

Kinase activity

Question 4

How do cyclin-Cdk complexes form?

Answer 4

by Cdk-activating kinase (CAK)

Question 5

How do cyclin-Cdk complexes become active?

Answer 5

After Cyclin binds to Cdk,

Cdk-activating kinase (CAK) phosphorylates Cdk

Question 6

Name the 4 types of cyclin (4)

Answer 6

D, E, A, B

Question 7

What does Cyclin D bind to?
What is the complex that forms?
What is the function of this complex?

Answer 7

• Cdk 4/6
• D-Cdk 4/6
• To pass the R-point at G1/S boundary

Question 8

What do Cyclins E and A bind to?
What are the complexes that form?
What is the function of these complexes?

Answer 8

• Cdk2
• E-Cdk2 and A-Cdk2
• To initiate DNA replication in early S phase

Question 9

What does Cyclin B bind to?
What is the complex that forms?
What is the function of this complex?

Answer 9

• Cdk1
• B-Cdk1
• Transition from G2 to M phase

Question 9

Chain of Cdk activation (4)

Answer 9

1) Cyclin D synthesised to active Cdk 4/6, in order to pass R-point

2) Cyclin E levels increase and activates Cdk2

3) E-Cdk2 activates A-Cdk2, which is required for DNA replications in S-phase

4) A-Cdk2 activates B-Cdk1 to allow cells to progress to M phase

Question 10

What is the checkpoint in G1?

Answer 10

Restriction point (R-point)

Question 11

What is the R-point controlled by?

Answer 11

Retinoblastoma protein (Rb)

Question 12

What is E2F?

Answer 12

Transcription factor for cell cycle advancement

Question 13

What is the function of Rb protein?

Answer 13

inhibition of E2F to prevent cell cycle advancement

Question 14

How does Rb inhibit the action of E2F?

Answer 14

• hypo-phosphorylated Rb is bound to E2F
• preventing E2F to express genes for cell cycle advancement

Question 15

How does Rb become inactivated? (3)

Answer 15

• hyper-phosphorylation of Rb
• releases E2F
• E2F can now express genes

Question 16

How does mitogenic signalling allow passing of R-point? (7)

Answer 16

1) Mitogenic signalling activates TFs such as AP-1

2) AP-1 binds to DNA and codes for cyclin D mRNA

3) Cyclin D mRNA translated to synthesise cyclin D

4) Cyclin D binds and activates Cdk 4/6

5) D-Cdk 4/6 phosphorylates Rb, which inactivates Rb and causes it to release its inhibition of E2F

6) E2F is now activated and induces gene expression

7) Cyclin E-Cdk2 hyper-phosphorylates Rb and inactivates it

Question 17

Function of Cdk inhibitors (CKIs)

Answer 17

bind to cyclin-Cdk complexes and block their action

Question 18

2 classes of CKIs

Answer 18

• INK4 (inhibits Cdk4)
• CIP/KIP (inhibits Cdk1/2)

Question 19

Target and Function of:
p16*INK4
(2)

Answer 19

• D-Cdk4/6
• prevents passage of R-point

Question 20

Target and Function of:
p21*CIP
(2)

Answer 20

• E-Cdk2 and B-Cdk1
• causes cell cycle arrest

Question 21

What happens in S-phase? (3)

Answer 21

• cells replicate DNA
• cells synthesis chromatin for packaging of DNA into chromosomes
• cyclin A-Cdk2 triggers events resulting in DNA replication

Question 22

What happens in G2 phase? (3)

Answer 22

• G2 is used to delay commitment of entering mitosis
• to grow in size and check if DNA is faultless
• cyclin B-Cdk1 is formed to allow cells to progress to M-phase

Question 23

M-phase:

Prophase and Metaphase (5)

Answer 23

Cyclin B-Cdk1 phosphorylates proteins which results in:

• condensing of DNA
• formation of mitotic spindle
• breakdown of nuclear envelope

Chromosome segregation requires correct attachment of sister chromatids to the spindle

Question 24

M-phase:

Metaphase (3)

Answer 24

• after attachment of sister chromatids to the spindle, chromosomes are tugged between the 2 poles, resulting in them moving to spindle equator
• unattached kinetochores to the spindle are detected by spindle assembly checkpoint which blocks entry to anaphase
• incorrect kinetochore attachment requires correction which causes chromosomes to lag in the spindle

Question 25

M-phase:

Anaphase and Telophase (4)

Answer 25

Separation of chromatids:

• the pull on kinetochores by the spindle is resisted by the cohesion of the chromatids
• chromatids are connected by cohesin proteins
• cyclin B-Cdk1 triggers the steps to cause breakdown of cohesin

Question 26

Upon mitogenic signalling, for each of the four phases of the cell cycle, name a main step or a control point and the relevant cell cycle regulator/protein.

Answer 26

G1: pass the R-point
- cyclin D-Cdk 4/6 deactivating Rb

S: DNA replication
- mediated by cyclin E-Cdk2 and A-Cdk2

G2: G2/M control point
- by the action of cyclin B-Cdk1

M: mitotic spindle forms
- by the action of cyclin B-Cdk1

Question 27

How does cell respond if DNA is damaged? (5)

Answer 27

1) Cells detect DNA damage and activates p53

2) p53 acts as a tumour suppressor and as a transcription factor

3) p53 causes expression of Cdk inhibitors (p21*CIP) halting the cell cycle

4) p53 also causes expression of DNA repair enzymes

5) p53 also expresses apoptotic proteins

Question 28

Describe how Capsases cause Apoptosis (4)

Answer 28

1) Capsases cleave proteins of the cytoskeleton, causing small blebs to form as membrane bulges out

2) Nucleus breaks apart and DNA breaks into small pieces

3) The cell breaks into several apoptotic bodies

4) The apoptotic bodies end up being cleared by macrophages through phagocytosis