Homework Questions

Question 1

Supplemental figure 1 shows a normal signaling pathway for the Ras protein acting under the control of an RTK. You are examining a mutated cell line with a constitutively active Ras protein, in which the Ras protein is always signalling. Which of the following conditions will cause the Ras protein to turn off?

Addition of a drug that prevents protein X from activating Ras

Addition of a drug that increases the affinity of the protein Y and Ras

Addition of a drug that increase the activity of protein Y

Addition of a drug that blocks protein Y from interacting with its target

Answer 1

Addition of a drug that blocks protein Y from interacting with its target

Question 2

In many types of cancer, hormone receptors are often overexpressed. Why would these receptors be beneficial to a tumorigenic cell?

Answer 2

Cancer cells need to proliferate, and hormones often transmit signals that cause cells to proliferate. Overexpressing receptors for these hormones could cause cancer cells to more actively grow, which is what they need to do to be cancer cells.

Question 3

Nuclear receptors…

are found only on the membrane of the nucleus.

only signal for transcriptional repressors.

respond to steroid molecule inputs.

directly control the rate of protein translation.

Answer 3

respond to steroid molecule inputs.

Question 4

Indicate whether the following statements are true or false. If false, correct the sentence.

Cell surface receptors that affect transcriptional regulation when activated display much faster response times than those that cause altered protein function.
In G-protein coupled receptors, a signal molecule will bind to the extracellular portion of the receptor and cause phosphorylation of a GDP molecule bound to the alpha subunit of the G-protein.
Enzyme-coupled receptors are typically dimerizable, such as receptor tyrosine kinases. These RTKs are often found to be mutated in cancer, as a mutation in only one receptor can cause massive changes downstream due to the outward-branching protein cascade they control.

Answer 4

a. False: Altered protein function can happen very quicky in the case of kinases phosphorylating another protein, so while it may be possible for there to be a protein alteration pathway that is slower than transcriptional regulation, that is going to be the less likely scenario

b. False: The signal molecule binding to the extracellular portion of the receptor causes GDP to dissociate from the alpha subunit, and GTP binds in its place.

c. True

Question 5

A very hot area of research in tissue engineering is the ‘washing’ of a donor organ, and repopulating it with a patient’s own cells to create a fully functioning, biocompatible organ for transplant recipients. The idea behind this is to wash the donor organ with a denaturing solution to clear away the donor cells, leaving a biological scaffold devoid of cells. The organ can then be seeded with a recipient patient’s cells, which will then infiltrate the structure left behind and differentiate to take on the role of cells native to the repopulated tissue. What type of material would you expect to be left in the organ scaffold left behind after removing the cells?

Answer 5

They type of material I would expect to be left behind is the extracellular matrix. This will have different compositions in different tissues, but is made primarily of fibrous proteins called collagens.

Question 6

During mitosis, microtubules originating from centromeres at either end of the cell line up towards the center of the cell. Why does this take place? Are these microtubules stabilized or dynamically unstable?

Answer 6

The microtubules are dynamically unstable until the nuclear envelope breaks apart and the ends of the the microtubules attach to the kinetochores on the centromeres of the chromosome. They are not guided there, it happens because the dynamic instability causes them to randomly encounter the kinetochores. Once they attach the kinetochores, the kinteochores act to stabilize the microtubules (they are no longer dynamically unstable), so that they all line up towards the center of the cell, with the chromosomes lined up in the center, attached to the mitotic spindle and ready to be separated.

Question 7

Intermediate filaments help protect animal cells from mechanical stress because __________.

Filaments directly extend from the interior of the cell to the extracellular space and into the next cell, linking one cell to the next, helping to distribute locally applied forces.

Filaments in each cell are indirectly connected to the filaments of a neighboring cell through the desmosome, creating a continuous mechanical link between cells.

Filaments remain independent of other cytoskeletal elements and keep the mechanical stress away from other cellular components.

Filaments make up the desmosome junctions that connect cells; these junctions are more important than the internal network of filaments for protecting cells against mechanical stress.

Answer 7

Filaments in each cell are indirectly connected to the filaments of a neighboring cell through the desmosome, creating a continuous mechanical link between cells.

Question 8

Muscle contraction involves __________.

The propagation of calcium ions from the extracellular space to the interior of muscle cells, causing contraction.

The hydrolysis of ATP to promote the dissociation of myosin heads from actin filaments, causing contraction.

Release of calcium ions from the sarcoplasmic reticulum, causing contraction.

The sliding of myosin filaments along actin filaments to produce mechanical force.

Answer 8

Release of calcium ions from the sarcoplasmic reticulum, causing contraction.

Question 9

Cancer cells often begin as epithelial tissue that has been mutated. One of the most frequent loss of function events that takes place during a transition from a normal to a cancerous state is the loss of E-cadherin, an epithelial specific cadherin protein. Why would this be advantageous for a cancer cell?

Answer 9

Cadherins help anchor cells together. If a cencerous cell loses its cadherin function, it is no longer firmly help in place, and can more freely move to another location in the body. This allows cancer to metastasize to other parts of the organ or body.

Question 10

During which phase of the cell cycle is a chromosomal translocation most likely to occur? Why?

Answer 10

A chromosomal translocation is most likely to occur during mitosis (M phase) when the chromosomes are held close together (in prophase, prometaphase), before they start to get pulled apart from each other during anaphase.

Question 11

In cells that divide infrequently, such as neurons or liver cells, at what rate would you expect cyclin G1 to accumulate? In rapidly dividing cells? Why?

Answer 11

In rapidly dividing cells, cyclin G1 would accumulate quickly. It is inactivated at the end of one mitosis division cycle, and cell division only happens again when enough cyclin G1 has accumulated. In cells that divide infrequently, this accumuation will happen very slowly.

Question 12

Progression through the cell cycle requires a cyclin to bind to a Cdk because __________.

the cyclins are the molecules with enzymatic activity in the complex.

the binding of a cyclin to Cdk is required for Cdk enzymatic acitivity.

cyclin binding inhibits Cdk activity until the appropriate time in the cell cycle.

]without cyclin binding, a cell-cycle checkpoint will be activated.

Answer 12

b. the binding of a cyclin to Cdk is required for Cdk enzymatic acitivity.

Question 13

The survival, [a], and size of each cell in an animal are controlled by extracellular signal molecules secreted by neighboring and distant cells. Many of these signal molecules bind to a cell-surface [b] and trigger various intracellular signaling pathways. One class of signal molecules, called [c], stimulates cell division by releasing the molecular brakes that keep cells in the [d] or [e] phase of the cell cycle. Members of a second class of signal molecules are called [f], because they stimulate cell growth and an increase in cell mass. The third class of signal molecules, called [g], inhibits [h] by regulating members of the [i] family of proteins.

Answer 13

Specified Answer for: a
proliferation
Specified Answer for: b
receptors
Specified Answer for: c
mitogens
Specified Answer for: d
G1
Specified Answer for: e
G0
Specified Answer for: f
growth factors
Specified Answer for: g
survival factors
Specified Answer for: h
apotosis
Specified Answer for: i
BcI2

Question 14

Programmed cell death may occur __________.

in both healthy and unhealthy or abnormal cells.

only by means of an intracellular suicide program.

rarely and selectively only during animal development.

only during embryonic development.

Answer 14

in both healthy and unhealthy or abnormal cells.

Question 15

The cells of a mammal’s germ line begin to differentiate from somatic cells several weeks after zygote formation. Why might it be advantageous for this differentiation to occur so quickly? What could happen if the germ line failed to separate out until an animal reaches sexual maturity?

Answer 15

It is beneficial for the gemr line to differentiate early because as cells divide, mutations become more likely to happen and accumulate. If the germ cell line went through many cell divisions before differentiating, the overall rate of mutations would be much higher, and the germ cells would be less likely to survive and be able to create healthy offspring.

Question 16

Indicate whether the following statements are true or false. If false, explain why or correct the statement.

Answer 16

Not yet graded, might not be right

Question 17

Indicate whether the following statements are true or false. If false, explain why or correct the statement.

Sexual reproduction leads to greater chances of survival because the gametes that carry alleles which enhance survival in harsh environments are passed on preferentially during meiosis and fertilization.
The process of division found in meiosis II is identical to that of mitosis.
Two genes close together on a chromosomal arm have an equally likely chance of independent assortment than genes far apart on the same arm during gamete formation.

Answer 17

Not yet graded, might not be right

a) False: alleles are split among the gamete cells more or less randomly (with neighboring parts of the chromosome more likely to be passed on together). The advantage of sexual reproduction comes from the rearragement of the chromosome in germ cells. Each offspring has a different combination of alleles, which allows for new combinations of traits that might prove to be more successful in harsh conditions. Additionally, it allows for more chances for unfavorable alleles to pass out of the gene pool altogether, if an unfavorable combination is passed on, it is less likely to survive to pass those alleles on again.

b) True: the process is exactly the same in meiosis II and mitosis (chromosomes line up at the spindle and are pulled apart into separate cells. However, the product is different. Mitosis results in two identical cells wiht a full complement of chromosomes, while meiosis II results in four non-identical haploid cells

c) False: the close they are together, the less likely there is to be crossover events between them. Genes that are right next to each other are very likely to be inherited together, while genes that are far away are very likely to have one or more crossover events between them, leading to an almost 50% chance of being separated

Question 18

As a scientist studying the latest pea plant technology, you decide that in your spare time you’d like to replicate some of Mendel’s classic crosses (say that 5 times fast). You cross two plants, one with homozygous for tall stature and white flowers, and one that is homozygous for short stature and purple flowers, to create the F1 generation. In this scenario, tall plants and purple flowers are dominant traits. You then cross two plants from the F1 generation to make the F2 generation. What is the chance of a plant in the F2 generation being heterozygous for the height gene, and homozygous recessive for flower color? Give your answer as a percentage, and round to two decimal places (i.e. 4.56% = 4.56).

Answer 18

12.5

Question 19

What percentage of tall plants with white flowers would you expect in the F1 generation? Give your answer as a percentage, and round to two decimal places (i.e. 4.56% = 4.56)

Answer 19

Not yet graded, might not be right

18.75

Question 20

During metaphase I of meiosis, the homologous chromosomes are held together by the __________.

bivalent.

chiasma.

proteins of the synaptonemal complex.

kinetochores.

Answer 20

chiasma.

Question 21

A pluripotent cell __________.

can only be produced in the laboratory.

is considered to be terminally differentiated.

can only give rise to stem cells.

can give rise to all the tissues and cell types in the body.

Answer 21

can give rise to all the tissues and cell types in the body.

Question 22

Where are induced pluripotent stem cells (IPSCs) derived from? How does this differ from the production of embryonic stem cells (ESCs)?

Answer 22

Induced pluripotent stem cells come from cells isolated from adult tissues that are cultured and transformed back into undifferentiated pluripotent stem cells. These are obtained very differently that embryonic stem cells, which come from an embryo and cause the embryo to be destroyed while obtaining them.

Question 23

One of the major reservations on using stem cells for in vivo therapies is their tumorigenic nature. Why would these cells be more likely to mutate into a cancerous state than other cell types?

Answer 23

Stem cells, especially when compared to terminally differentiated cells, tend to proliferate and divide rapidly, making it more likely for mutations to happen and for cancer to develop. They can develop into a tumor called a teratoma. Differentiated cells divide much less often, and are suscptible to the regulatory signals in that organ, so are less likely to mutate and begin to divide rapidly.

Question 24

After isolating either ESCs or IPSCs, what are the most important factors in differentiating the cells into useful tissue types?

Answer 24

Stem cells need the right environmental signals to differentiate, and these environmental signals need to come at the right time for those cells. Differentiating them into the correct and useable tissue types involves delivering the right growth factors in the media at the right schedule, as well as providing the correct structure to the physical environment. Certain organs need the right mechaincal or electrical signals to develop correctly. Gene expression is not useful alone if the tissue doesn’t develop with the correct structure to be useful.

Question 25

KRAS is a gene commonly found to be mutated in several different types of cancer. It is activated through the dimerization of a receptor tyrosine kinase in response to growth factors, and causes the cell to upregulate glucose intake. KRAS is typically mutated to be constitutively active in cancer patients.

How might the constitutive activation of KRAS aid in the development of a tumorigenic state in a cell?
What would be the effect on a cell if only one copy of the KRAS protein was mutated? Both copies?
Which of the two classes of cancer-related genes is KRAS? How can you tell?

Answer 25

1) by increasing glucose intake into a cell, this will provide the cell wtih an abundance of energy to grow and divide, which a cancer cell needs

2) If only one copy of the KRAS protein is mutated it will still upregulate glucose intake. This is a gain-of-function mutation, and usually is dominant, and only requires one copy of the gene to cause the phenotype, which in this case commonly results in cancer. If both copies were mutated the effect would likely be a bit stronger, but not markedly different.

3) This is a proto-oncogene. It does not inhibit cancer, but when its activity is increased it can cause cancer (as an oncogene)

Question 26

One of the hallmarks of cancer discussed in class is a cancer cells ability to replicate seemingly endlessly. In these cells, telomerase is typically upregulated.

What is the function of telomerase?
How does this aid in multiple cell divisions, and ultimately a tumorigenic state?

Answer 26

a) telomerase maintains the telomeres at the end of the chromosomes. The telomeres shorten each time a cell divides and when the telomeres get too short, the cell stops dividing. Telomerase keeps the telomeres from shortening too much.

b) Upregulated telomerase allows cells to divide more times before they stop dividing and die. This allows the cancer to grow much more and divide many more times than a cell normally would be able to, increasing the likelihood of cancer.

Question 27

Many chemotherapeutic drugs are not only toxic to cancer cells, but can actually make the patient very sick due to large scale death of healthy tissue as well. Why do you think it is so difficult to directly target cancer cells while avoiding healthy cells?

Answer 27

Many aspects of cancer cells are identical to normal healthy cells. While there are sometimes single dramatic mutations that differentiate them from healthy tissue, cancer is most often caused by normal cell processes that are expressing themselves at inappropriate times and locations. Or, alternatively, an accumulation of mutations that alone would not cause an issue, but together cause uncontrolled cell growth. Is it thus very difficult to target only the cancer cells in a body, as many of the targeted proteins are also present in normal healthy cells, just in different quantities.

Question 28

What is a checkpoint blocker and how does this type of therapy work? Why is it most successful against cancers with high mutation burdens?

Answer 28

Checkpoint inhibitors physically block CTLA4 of PD-1/PDL-1, which provides feedback to the T-cells and prevents an unregulated immune response. When cancer cells bind to either of these proteins, it downregulates T-cell activity, allowing the cancer cells to grow unchecked by the immune system. The checkpoint inhibitors, which are often antibodies, block this interaction and allow the T-cells to proceed as normal, identifying the cancer cells and killing them.

These checkpoint blockers work best against cancers with high mutation rates because those ones are more likely to be recognized as tumor cells by the immune system. A cancer cell with only one mutation is much less likely to be recognized as abnormal.