Cancer is thought to be caused by the accumulation of two or more \"hits\" that
ID: 15279 • Letter: C
Question
Cancer is thought to be caused by the accumulation of two or more "hits" that is, two or more mutations that affect cell proliferations and survival in the same cell. Many of these oncogenic mutations are dominant: one mutant copy of the gene is sufficient to change the proliferative properties of a cell. Which of the following general types of mutations have the potential to create dominant oncogenes? Justify each answer.a. a mutation that increases the number of copies of a transcriptional activator of cyclin A
b. a nonsense mutation located shortly after the beginning of translation in a gene that encodes a growth-factor receptor
c. a mutation that increases the level of FasL
d. a mutation that disrupts the active site of a cytoplasmic tyrosine-specific protein kinase
e. a translocation that joins a gene encoding an inhibitor of apoptosis to an enhancer element for gene expression in the liver
Explanation / Answer
The correct options are option A and E.
A. Cyclin A is a protein that interacts with cyclin dependent kinases and activate their enzyme activity. During S phase, when sufficient number of cyclin A molecules accumulate in cells, they form complex with CDK2. This complex inhibits the function of cyclin E/CDK2, and it initiates DNA replication. Cyclin A also ensure that the DNA replicates only once per cell cycle. However, if a mutation causes an increase in the number of copies of transcriptional activator of cyclin A, more cyclin A are produced in the cell. This may lead to continuous replication of DNA of loss of cell cycle regulation.
E. a translocation that joins a gene encoding an inhibitor of apoptosis to an enhancer element for gene expression in the liver: the translocation is likely to enhance the expression of inhibitor of apoptosis. Inhibitors of apoptosis block the intrinsic pathway of apoptosis which can lead to cancer since they deregulate the cell cycle.
B. Growth factor receptor is required for initiation of cell division. If a non-sense mutation occurs at the beginning of translation in a gene that encodes growth-factor receptor, the ligand cannot bind it since a non-sense mutation causes termination of chain elongation. Therefore, this mutation cannot lead to cancers.
C. Interaction of FasL with Fas leads to apoptosis of the cell. If FasL is increased, the cell is more susceptible to apopsotis.
D. Tyrosine – specific protein kinases can attach phosphate groups to certain amino acids like tyrosine, serine, and threonine. Protein tyrosine kinases, if remain in the active state, can cause unregulated cell growth. However, if the active site of the enzyme is disrupted, it cannot function and hence, cannot activate cell cycle
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