Cell replication

Question 1

What are the two parts of M phase

Answer 1

The M phase of the cell cycle consists of the mitosis and then the cytokinesis

Question 2

How often do intestinal epithelial cells and hepatocytes divide

Answer 2

Intestinal epithelial stem cells divide around every 20 hours, whereas hepatocytes divide roughly once per year

Question 3

Which cells do not divide anymore

Answer 3

Neurones and cardiac myocytes cannot divide

Question 4

What are the four stages of the cell cycle

Answer 4

The four stages are G1, S, G2 and M phase

Question 5

When does cell go into quiescent phase

Answer 5

In absence of a growth stimulus, cells go into G0 phase

Question 6

What signals must cell get to get past checkpoint in cell cycle

Answer 6

It must get the information that their are stimulant growth factors, that there are sufficient nutrients and that last phase has been completed succesfully. This will be done via cyclins.

Question 7

Which kind of receptors are involved in growth factor stimuli

Answer 7

Enzyme linked tyrosine kinase receptors are involved in growth factor stimuli for cell growth and replication

Question 8

What are four growth factor pathways in cells

Answer 8

Ras, Raf, ERK, MEK are growth factor signalling pathways in cells

Question 9

What is the effect of growth factors on cell

Answer 9

Growth factors indirectly increase protein synthesis and decrease protein degradation. They stimulate the entry of cell cycle from G0 to G1 by inducing the expression of c-Myc

Question 10

Which molecule drives G0 to G1 transition

Answer 10

c-Myc, which is expressed in response to growth factor stimuli

Question 11

What is the function of c-Myc

Answer 11

c-Myc is a transcription factor of genes that are involved in the cell cycle

Question 12

In what cells is c-Myc overexpressed

Answer 12

In tumour cells c-Myc is overexpressed which leads to aberrant cell replication

Question 13

Which amino acid residues can be phosphorylated

Answer 13

Serine, threonine and tyrosine residues can be phosphorylated by kinases because they contain hydroxyl groups

Question 14

What are CDK’s

Answer 14

Cyclin dependent kinases are enzymes that only function when bound to cell cycle stage dependent kinases and are involved in the progression of the cell cycle

Question 15

Where can CDK’s be found

Answer 15

CDK’s can be found in all proliferating cells in relatively constant concentrations

Question 16

Why are cyclins called cyclins and when is the concentration in cell high

Answer 16

Cyclins are proteins which concentrations fluctuates according to the phase of the cell cycle

Question 17

What happens to cyclins after mitosis

Answer 17

Cyclins are degraded after they have exerted their function

Question 18

Why are there checkpoints in cell replication cycle

Answer 18

To prevent the replication of cells that contain genetic defect that can no longer function properly

Question 19

What three reasons are protein kinase cascades used for

Answer 19

Protein kinase cascades allow for amplification of a signal, for diversification of that signal and for regulation of signals

Question 20

Why are protein kinase cascades used in cell cycle

Answer 20

Protein kinase cascades are used in cell cycle because it provides a good opportunity to regulate the signalling pathways involved in cell replication

Question 21

By what enzymes is protein kinase cascade inactivated

Answer 21

Phosphatases can inactivate protein kinases by dephosphorylation

Question 22

Which two things regulate CDK activity

Answer 22

CDK activity is determined by their interaction and presence of cyclins and phosphorylation of the CDK

Question 23

How does CDK and cyclin concentration change in proliferating cell

Answer 23

CDK concentrations in proliferating cells is relatively constant, whereas cyclin concentration varies depending on specific expression on various point in cell cycle

Question 24

What are the three stages of CDK activation

Answer 24

1. The binding of cyclin to the right CDK to form an inactive CDK-cyclin complex, 2. the double phosphorylation of this complex which is still inactive, 3 the removal of the inhibitory phosphate by activating protein phosphatase to produce an active CDK-cyclin complex

Question 25

How does positive feedback in CDK drive cell cycle forwards

Answer 25

Active CDK-cyclin complexes can activate the activating phosphatases required in the last step of CDK activation to produce more active CDK and this can also inactivate the inhibitory kinase which can inhibit the second step of phosphorylation in the activation process. The effect is very rapid increase of active CDK-cyclin complexes needed for cell cycle progression.

Question 26

What are the triggers for the induction of S- and M-phase in cell cycle

Answer 26

The formation of S-Cdk complexes induced by other Cdk-complexes triggers S-Phase, the formation of M-Cdk complexes induced by other Cdk-complexes triggers M-phase

Question 27

How is cyclin inactivated and how does this degradation make concentration cyclic

Answer 27

Cyclins are degraded for inactivation and because the concentrations increase through expression and decrease through degradation the concentrations are cyclic

Question 28

Which cellular mechanism carries out ubiquitylation/ubiqutination

Answer 28

The proteosome of the cell detects cyclins that have been ubiquinated and degrades these cyclins, which inactivates the CDK

Question 29

What is the function of CDK’s sequentially stimulating the synthesis of genes for next phase

Answer 29

The sequential stimulation of CDK’s to induce activation of next CDK gives timing and direction to the cell cycle

Question 30

Where was retinoblastoma protein first identified

Answer 30

In children with tumour on the retina

Question 31

What is mitogen signalling

Answer 31

Mitogen signalling is growth factor signalling that results in the cell growth and cell cycle process needed for replication

Question 32

What transcription factors does Rb protein bind to

Answer 32

Retinoblastoma protein binds to E2F transcription factors and inhibits their function, where they would normally promote transcription of proteins that are required for cell replication and the cell cycle

Question 33

Which important proteins for cell replication are inhibited if E2F transcription factors are inactive

Answer 33

DNA polymerase and thymidine kinase are produced from genes that are promoted by E2F transcription factors, so these are inhibited when E2F is inhibited

Question 34

How does CDK inactivate Rb protein and how does this enable transcription

Answer 34

By phosphorylating Rb, Rb dissociated from the transcription factor which can then promote gene transcription

Question 35

In which order are the cyclins expressed in the cell cycle

Answer 35

D, E, A, B. D expressed in G1, E in G1 and S, A in S G2 and M and B in M

Question 36

What is the function of protein p53

Answer 36

p53 is involved in arresting cell cycle progression in G1 when DNA damage is detected, which can then be repaired before cell progresses to S-phase where otherwise damaged DNA would be replicated

Question 37

What is the difference in activated p53 and inactive p53

Answer 37

Activated p53 is phosphorylated and becomes more stable than inactive p53, which is constantly being turned over in the cell

Question 38

How is p53 activated and how is degraded

Answer 38

p53 is activated by protein kinases when DNA damage is detected, and normally in its unstable form it is degraded by proteasomes

Question 39

For what gene is activated p53 the transcription factor

Answer 39

Activated p53 can serve as a transcription factor for the transcription of mRNA for p21

Question 40

What is the function of the P21 proteins

Answer 40

p21 is a CDK inhibitor that binds to the CDK-cyclin complex to inactivate it to arrest the cell cycle

Question 41

Which membrane receptor is overly active in many breast cancers

Answer 41

The HER2/EGFR receptor is often overly active in many breast cancers

Question 42

What does the drug Herceptin do in breast cancers

Answer 42

It blocks the tyrosine kinase pathway that this overly active EGFR receptor uses to induce malignant growth of cells

Question 43

Which two oncogenes are very often overexpressed in many different cancers

Answer 43

c-Myc and Ras are often overexpressed in many different cancers

Question 44

What cyclin is often over-expressed in breast cancers

Answer 44

Cyclin D is often expressed in mutant form in breast cancers

Question 45

Which tumour suppressor is inhibited in more than 50% of tumours

Answer 45

In more than 50% of tumours p53 has lost its function through mutations

Question 46

What is the difference in mutation consequence between oncogenes and tumour suppressors

Answer 46

Mutations that have an effect on tumour suppressors can be considered as recessive because both copies have to be mutated to cause consequence of loss of function, whereas oncogenic mutations can be considered dominant because a gain of function mutation already occurs when one copy of a gene is mutated