Cell replication

Question 1

When are cells in G0 (quiescent phase)?

Answer 1

In absence of stimulus, cells go into G0

or

differentiated cells (neurones, hepatocytes)

Question 2

What causes cells to leave G0?

Answer 2

In response to growth factors ( extracellular factors )

Signal amplification

Signal integration/modulation from other pathways

Ras/Raf/MEK/ERK

Question 3

Examples of signalling proteins? (If these are mutated cancer risk increases)

Answer 3

Ras/Raf/MEK/ERK

Question 4

How does a cell transition from G0 to G1?

Answer 4

growth factor stimulate c-Myc - a transcription factor

acts as a oncogene

c- Myc : growth factor signalling pathways induces expression of c-Myc. stimulates expression of cell cycle

Question 5

What are Cyclin-dependent Kinases?

Answer 5

They are found inactive in proliferative cells.

Become activated when a cyclin binds

They phosphorylate molecules to activate or inactivate a protein

molecule examples : serine / threonine / tyrosine

Question 6

Why can Serine, Threonine and Tyrosine be phosphorylated?

Answer 6

Due to their hydroxyl groups

Question 7

What causes production and degradation, the levels of cyclins or the levels of CDKs?

Answer 7

Levels of cyclin as they fluctuate.

CDKs are always present in same concentration

Only the cyclin : Cdk complex is active during mitosis

Question 8

What CDK does cell cycle entry require?

Answer 8

C-Myc promotes CDK4/6 - Cyclin D complex

Allows progression to S phase

Question 9

Why are protein Kinase Cascades useful?

Answer 9

Kinases can be regulated by other kinases and this can cause both signal amplification/diversification of pathways or an opportunity for regulation

Question 10

What causes a CDK-Cyclin complex to go from inactive to active?

Answer 10

The CDK has inhibitory phosphates and activating phosphates both bound to it

An activating protein phosphatase needs to remove the inhibitory phosphate

a cyclin will join a CDK but the complex is inactive

an activating protein phosphatase will remove the inhibitory phosphate on the CDK

activate + positive feedback

Question 11

How are Cyclins removed from the CDK-Cyclin complex?

Answer 11

Ubiquitylation of cyclin ( signal on Cyclin that represents destroy me)

leaving a inactive CDK

Question 12

How do CDKs-Clyclins regulate expression of the next complex?

an example?

Answer 12

Once active they stimulate synthesis of genes required for next phase.

e.g.
( G1 ) Cdk4/6-cyclin D leads to
( S ) Cdk2-cyclin E leads to 
(G ) Cdk2-cylin A leads to 
( mitosis ) Cdk1-cyclin B

Question 13

How is cell growth carried out?

Answer 13

Intracellular signalling pathways which drive proteins synthesis increase levels of proteins and since protein degradation is inhibited there is a net increase in protein.

Question 14

How does Retinoblastoma protein act as a brake on cell proliferation?

Answer 14

isolates transcription factor in an inactive form so cannot turn on genes needed for cell cycle progression

Tumors seen in eyes in childhood if the Rb protein is MISSING as there is a lack of a tumour supprssor

Question 15

How does the Rb brake become released?

Answer 15

Phosphorylation of Rb by G1-Cdk / G1/S-Cdk complexes

Inactivates Rb releasing transcription factor, allowing translation and cell proliferation

Question 16

What is E2F and why is it important?

Answer 16

It is a transcription factor

Allows cell cycle progression once Rb is inactivated. Allows Cyclin E to bind to Cdk2 for S phase to begin

Question 17

What if there are cells with damaged DNA in G1?

What does inactive p53 do?

Answer 17

p53 recognises the break in the DNA and protein kinases are activated.

These phosphorylate p53 activating it.

Question 18

What does active p53 do?

Answer 18

In presence of DNA damage it binds to regulatory region of p21 gene. transcribing p21 mRNA = p21 protein

Question 19

What does the p21 family do?

Answer 19

Inhibits Cyclin-Cdk complexes by binding to it

Question 20

What examples of overexpression can cause cancer?

Answer 20

Regulatory proteins e.g. 
Ras
Cyclin D1
C-Myc
EGFR/HER2

Question 21

What examples of loss of expression can cause cancer?

Answer 21

Regulatory proteins such as suppressors
Rb ( lung cancers )
p53 ( all human cancers, need mutation of both copies of the gene)

Question 22

Extra missed info?

Answer 22

Cell cycle : duplication , division, co-ordination

• interphase : G1 + S + G2
• Cell cycle checkpoints (5) : external environment must have nutrients and growth factors,

G1 checkpoint : is enironment favourable = enter S phase

G2 checkpoint : is dna replicated, is dna damage repaired = enter mitosis

Mitosis checkpoint : are chromosomes properly attached to mitotic spindle = pull apart chromosomes

If repair cannot work undergo apoptosis

Growth factor ( mitogen signalling ) - for cell doubling in size