Final Exam Flashcards
How come we don’t carry thousands of tumors?
It is difficult to transform human cells.
We have caretakers, immune system, and our cells need to accumulate mutations to transform.
Where would we find the cancerous mutations?
Stem cell compartment.
Because stem cells would retain cancerous mutations and pass to later generation of cells.
How are stem cells protected from mutations/ harmful environment?
- They are isolated anatomically
- They divide, but not very often
- There are DNA repair systems that will either fix errors or call for cell cycle arrest/apoptosis.
- There are additional mechanisms to protect cells.
True or False
One mutation is enough to cause cancer in human.
False.
Cancer requires accumulation of mutations
True or False
A single tumor contains only 1 population of cells with the same mutations.
False.
A single tumor contains various populations of cells with different mutations.
Why is it a challenge for scientists to effectively treat a tumor?
There are many different mutations within a tumor, and it is hard to find a drug that targets all kinds of mutations in a tumor.
True or False
Every cancerous cell has tumorigenic capability.
False.
Only some, not all.
What could have promoted the increased mutation rate?
Mutations in caretaker genes (ex: p53)
What are the problems that can caused by chromosomal translocation?
- Cut off important genes
- Silencing tumor suppressor genes.
- Overexpressing oncogenic activity
What is the property of chromosomes in cancer cells?
It accumulates abnormalities (translocation)
What are two signals that activate p53? What are two outcomes of p53 activation?
Signals: DNA damage, hyperproliferative stress
Outcomes: cell cycle arrest, apoptosis.
SV40 DNA virus can cause transformation of monkey kidney cells or murine cells into cancerous cells, what would be your approach to identify the protein that promote transformation?
- Design two groups: experimental group (infected with the virus) and control group (not infected).
- Collect blood serum from two groups. Experimental group should contain antibodies to viral proteins.
- Infect another cells with the virus and use blood serum from experimental group to identify the viral protein that causes transformation (immunoprecipitation)
- Perform western blot and see the different between two groups (differential display)
Why is p53 firstly hypothesized as proto-oncogene?
It is expressed in low concentration in normal cells.
What is the function of p53?
Transcription factor that acts to inhibit tumor progression.
What effect does T antigen from SV40 virus have on p53?
T antigen sequesters p53.
p53 is only active in what form?
homotetramer.
A dominant-negative mutation of p53 can induce cancer in cell culture, does this mean that heterozygotes (+/-) do not need a second mutation for tumor progression?
There is still 1 functional p53 homotetramer out of 16 p53 homotetramer. Hence, it is enough to perform normal function which is inhibit tumor progression.
Which type of mutation is the most common p53 mutations in cancer patients?
Missense mutations
Which p53 domain region are highly mutated?
DNA binding domain
True or False
Homozygote mutant p53(-/-) mice can complete embryogenesis.
True
p53 might not be needed during embryogenesis, and there are other tumor suppressor genes.
What is the risk of inherited germ-line mutations in p53?
Cause predisposition for distinct cancer in variable ages, aka p53 is universal.
Li-Fraumeni syndrome.
What is the expression of p53 in normal cells?
Low
What effect does increasing exposure to UV on p53 protein levels?
p53 protein levels increase upon exposure to UV.
Why would the T antigen sequester p53 if the cells behave normally upon viral infection.
Viral infection causes the cell to hyperproliferate by sequestering pRb (check point) by T antigen, therefore, hyperproliferation might cause activation of p53 which prevent the cell from proliferating. Therefore, T antigen also needs to sequester p53.
Achieve high proliferation in host cells.
How does the cell achieve low concentrations of p53 protein?
p53 is degraded very fast via the ubiquitine system.
TRUE or FALSE
p53 is only needed occasionally, therefore, p53 is not always synthesized.
False.
p53 is always synthesized all the time
Synthesizing protein consumes a high amount of energy; however, p53 is constantly be made and degraded. Why might this be the case?
p53 plays such a critical role in the cell, so it needs to be present all the time to immediately response when the cell needs it.
Also, inhibiting degradation of p53 is easier than synthesizing new p53 proteins.
Which E3 ligase ubiquitinate p53 protein?
MDM2
What is transcriptional factor that drives the transcription of MDM2?
p53
p53 activates its own downregulation pathway
If you have a missense mutant p53 (where it cannot bind to DNA efficiently). Do you expect to have a higher/ same/ or lower levels of p53 compared to wildtype?
Higher levels of p53 because it cannot bind to DNA therefore MDM2 cannot be made to degrade p53,
MDM2 is regulated by p53, andd MDM2 degrades/ubiquitinate p53.
What are two agents induce p53 activity?
- DNA damage
- Hyperproliferative stress
What is the different between ATM and ATR?
ATM is responsible to fix the damage causes to both strands of DNA.
ATR is responsible to fix the damage causes to only one strand of DNA.
What are ATM and ATR classified as?
Ser/Thr kinases
How does ATR activate Chk1?
ATR bind to the damage site, then it recruits proteins, phosphorylates them and form a complex. The complex then recruits Chk1, and Chk1 is activated via phosphorylation by ATR.
Do not need to know the name of some proteins
True or False
Phosphorylation is required for p53 to be active.
False.
It is not needed.
What is the purpose of phosphorylating p53 by Chk1?
MDM2 cannot bind to phosphorylated p53, and p53 cannot be degraded.
What are two phosphorylation targets of Chk1?
p53 (prevent MDM2 from binding)
MDM2 (inactivate it)
Expression of which gene tells us that we have crossed the R point in the cell cycle?
E2F
Which protein induce the transcription of the ARF gene?
E2F
What is the function of ARF?
ARF binds to and sequesters MDM2
What does high activity of E2F tell you?
The cell is hyperproliferative.
What is a problem when both p16 and ARF are located in the same locus?
Mutation in that locus will disrupt the function of both genes.
How are cancer and evolution related to each other?
Mutation on oncogene and tumor suppressor gene reduce one’s fitness (unable to reproduce). Therefore, evolution will work agains mutations by providing more genes to fight against cancer.
Radiation used as a therapy treatment for cancer
The spleen is more radiosensitive than the intestine. What would you expect to see if we compare p53 stability between spleen and intestine?
Spleen would have better p53 stability since it is more susceptible to DNA damage caused by radiation.
Radiation used as a therapy treatment for cancer
How could you “help” the intestine to have a more sustained p53 response?
Design a drug to inhibit the MDM2 => increase stability of p53
block p53 inhibitor
Which CKI is regulated by p53?
CKI p21
Why does p53 regulate p21, but not p16 in the cell cycle?
p21 controls the part of the cell cycle where DNA damages highly occur.
CKI p21 belong to what CKI families?
Cip/Kip