Cell replication Flashcards
What are the two parts of M phase
The M phase of the cell cycle consists of the mitosis and then the cytokinesis
How often do intestinal epithelial cells and hepatocytes divide
Intestinal epithelial stem cells divide around every 20 hours, whereas hepatocytes divide roughly once per year
Which cells do not divide anymore
Neurones and cardiac myocytes cannot divide
What are the four stages of the cell cycle
The four stages are G1, S, G2 and M phase
When does cell go into quiescent phase
In absence of a growth stimulus, cells go into G0 phase
What signals must cell get to get past checkpoint in cell cycle
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.
Which kind of receptors are involved in growth factor stimuli
Enzyme linked tyrosine kinase receptors are involved in growth factor stimuli for cell growth and replication
What are four growth factor pathways in cells
Ras, Raf, ERK, MEK are growth factor signalling pathways in cells
What is the effect of growth factors on cell
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
Which molecule drives G0 to G1 transition
c-Myc, which is expressed in response to growth factor stimuli
What is the function of c-Myc
c-Myc is a transcription factor of genes that are involved in the cell cycle
In what cells is c-Myc overexpressed
In tumour cells c-Myc is overexpressed which leads to aberrant cell replication
Which amino acid residues can be phosphorylated
Serine, threonine and tyrosine residues can be phosphorylated by kinases because they contain hydroxyl groups
What are CDK’s
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
Where can CDK’s be found
CDK’s can be found in all proliferating cells in relatively constant concentrations
Why are cyclins called cyclins and when is the concentration in cell high
Cyclins are proteins which concentrations fluctuates according to the phase of the cell cycle
What happens to cyclins after mitosis
Cyclins are degraded after they have exerted their function
Why are there checkpoints in cell replication cycle
To prevent the replication of cells that contain genetic defect that can no longer function properly
What three reasons are protein kinase cascades used for
Protein kinase cascades allow for amplification of a signal, for diversification of that signal and for regulation of signals
Why are protein kinase cascades used in cell cycle
Protein kinase cascades are used in cell cycle because it provides a good opportunity to regulate the signalling pathways involved in cell replication
By what enzymes is protein kinase cascade inactivated
Phosphatases can inactivate protein kinases by dephosphorylation
Which two things regulate CDK activity
CDK activity is determined by their interaction and presence of cyclins and phosphorylation of the CDK
How does CDK and cyclin concentration change in proliferating cell
CDK concentrations in proliferating cells is relatively constant, whereas cyclin concentration varies depending on specific expression on various point in cell cycle
What are the three stages of CDK activation
- 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
How does positive feedback in CDK drive cell cycle forwards
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.
What are the triggers for the induction of S- and M-phase in cell cycle
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
How is cyclin inactivated and how does this degradation make concentration cyclic
Cyclins are degraded for inactivation and because the concentrations increase through expression and decrease through degradation the concentrations are cyclic
Which cellular mechanism carries out ubiquitylation/ubiqutination
The proteosome of the cell detects cyclins that have been ubiquinated and degrades these cyclins, which inactivates the CDK
What is the function of CDK’s sequentially stimulating the synthesis of genes for next phase
The sequential stimulation of CDK’s to induce activation of next CDK gives timing and direction to the cell cycle
Where was retinoblastoma protein first identified
In children with tumour on the retina
What is mitogen signalling
Mitogen signalling is growth factor signalling that results in the cell growth and cell cycle process needed for replication
What transcription factors does Rb protein bind to
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
Which important proteins for cell replication are inhibited if E2F transcription factors are inactive
DNA polymerase and thymidine kinase are produced from genes that are promoted by E2F transcription factors, so these are inhibited when E2F is inhibited
How does CDK inactivate Rb protein and how does this enable transcription
By phosphorylating Rb, Rb dissociated from the transcription factor which can then promote gene transcription
In which order are the cyclins expressed in the cell cycle
D, E, A, B. D expressed in G1, E in G1 and S, A in S G2 and M and B in M
What is the function of protein p53
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
What is the difference in activated p53 and inactive p53
Activated p53 is phosphorylated and becomes more stable than inactive p53, which is constantly being turned over in the cell
How is p53 activated and how is degraded
p53 is activated by protein kinases when DNA damage is detected, and normally in its unstable form it is degraded by proteasomes
For what gene is activated p53 the transcription factor
Activated p53 can serve as a transcription factor for the transcription of mRNA for p21
What is the function of the P21 proteins
p21 is a CDK inhibitor that binds to the CDK-cyclin complex to inactivate it to arrest the cell cycle
Which membrane receptor is overly active in many breast cancers
The HER2/EGFR receptor is often overly active in many breast cancers
What does the drug Herceptin do in breast cancers
It blocks the tyrosine kinase pathway that this overly active EGFR receptor uses to induce malignant growth of cells
Which two oncogenes are very often overexpressed in many different cancers
c-Myc and Ras are often overexpressed in many different cancers
What cyclin is often over-expressed in breast cancers
Cyclin D is often expressed in mutant form in breast cancers
Which tumour suppressor is inhibited in more than 50% of tumours
In more than 50% of tumours p53 has lost its function through mutations
What is the difference in mutation consequence between oncogenes and tumour suppressors
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
